UNIVERSITY  OF  CALIFORNIA 
SAN  FRANCISCO  LIBRARY 


TEXT-BOOK  OP 


EMBRYOLOGY 


BY 


FREDERICK  RANDOLPH  BAILEY,  A.  M.,  M.  D. 


FORMERLY  ADJUNCT  PROFESSOR  OF  HISTOLOGY  AND  EMBRYOLOGY,  COLLEGE  OF  PHYSICIANS  AND 
SURGEONS  (MEDICAL  DEPARTMENT  OF  COLUMBIA  UNIVERSITY) 


AXD 


ADAM  MARION  MILLER,  A.  M. 

INSTRUCTOR   IN    ANATOMY,    COLLEGE    OF   PHYSICIANS    AND   SURGEONS    (MEDICAL 
DEPARTMENT   OF   COLUMBIA   UNIVERSITY) 


Second  BOition 


WITH 
FIVE  HUNDRED  AND  FIFTEEN  ILLUSTRATIONS 


NEW  YORK 
WILLIAM  WOOD  AND  COMPANY 

MDCCCCXI 


COPYRIGHT,  1911, 
BY  WILLIAM  WOOD  &  COMPANY. 


Printed  by 

The  Maple  Press 

York.  Pa. 


PREFACE  TO  THE  SECOND  EDITION 


The  generally  favorable  criticisms  with  which  the  first  edition  of  the  text- 
book has  been  received  and  the  necessity  for  a  second  edition  in  two  years  is 
gratifying.  If  its  reception  may  serve  as  a  criterion  of  its  usefulness  as  a  book 
intended  primarily  for  the  student  of  medicine,  it  is  fulfilling  the  main  pur- 
pose of  its  authors. 

In  the  present  edition  some  errors  have  been  corrected  and  some  para- 
graphs have  been  rewritten,  owing  to  the  fact  that  important  advances  have 
been  made  in  the  science  even  in  the  brief  time  elapsing  between  the  two 
editions.  There  has  been  however  no  change  in  the  general  plan  and  scope 
of  the  work,  as  outlined  in  the  preface  to  the  first  edition. 

THE  AUTHORS. 
AUGUST  15,  1911. 


zii 


5 Or*, 
vu  «> 


PREFACE  TO  THE  FIRST  EDITION 


The  Text-book,  as  originally  planned,  is  an  outgrowth  of  the  course  in 
Embryology  given  at  the  Medical  Department  of  Columbia  University.  It  was 
intended  primarily  to  present  to  the  student  of  medicine  the  most  important 
facts  of  development,  at  the  same  time  emphasizing  those  features  which 
bear  directly  upon  other  branches  of  medicine.  As  the  work  took  form,  it 
seemed  best  to  broaden  its  scope  and  make  it  of  greater  value  to  the  general 
student  of  embryology  and  allied  sciences.  With  the  opinion  that  illustrations 
convey  a  much  clearer  conception  of  structural  features  than  verbal  description 
alone,  the  writers  have  made  free  use  of  figures. 

The  plan  of  adding  brief  "Practical  Suggestions"  at  the  end  of  each  chapter 
has  been  so  thoroughly  satisfactory  in  the  Text-book  of  Histology,  especially 
in  connection  with  laboratory  work,  that  it  has  been  adopted  here.  These 
"suggestions"  are  not  intended  to  be  complete  descriptions  of  embryological 
technic,  but  are  for  the  purpose  of  furnishing  the  laboratory  worker  with  cer- 
tain of  the  more  essential  practical  hints  for  studying  the  structures  described 
in  the  chapter.  To  avoid  frequent  repetition,  some  of  the  best  methods  of 
procuring,  handling,  and  preparing  embryological  material,  and  some  of  the 
more  important  formulae  are  given  in  the  Appendix,  which  is  intended  to  be 
used  mainly  for  the  carrying  out  of  the  "Practical  Suggestions." 

The  development  of  the  Germ  Layers  has  been  treated  rather  elaborately 
from  a  comparative  standpoint,  because  this  has  been  found  the  most  satisfac- 
tory method  of  teaching  the  subject. 

In  the  chapter  on  the  Nervous  System  the  aim  has  been  to  give  a  general 
conception  of  the  subject,  which,  if  once  mastered  by  the  student,  will  give 
him  an  insight  into  the  structure  and  significance  of  the  nervous  system  that 
will  bring  this  difficult  subject  more  fully  within  his  grasp. 

In  Part  II  (Organogenesis) ,  at  the  end  of  each  chapter  there  is  given  a  brief 
description  of  certain  developmental  anomalies  which  may  occur  in  connection 


VI  PREFACE. 

with  the  organs  described  in  the  chapter.  In  Chapter  XIX  (Teratogenesis) 
the  nature  and  origin  of  the  more  complex  anomalies  and  monsters  are  dis- 
cussed, and  also  the  causes  underlying  the  origin  of  malformations. 

The  writers  wish  to  thank  Dr.  Oliver  S.  Strong  for  his  painstaking  work  on 
the  chapter  on  the  Nervous  System.  Dr.  Strong  in  turn  wishes  to  acknowledge 
his  indebtedness  to  Dr.  Adolf  Meyer  for  important  ideas  underlying  the  treat- 
ment of  his  subject,  and  also  for  many  valuable  details.  He  expresses  his 
thanks  also  to  Professors  C.  J.  Herrick,  H.  von  W.  Schulte  and  G.  L.  Streeter 
for  helpful  criticisms  and  suggestions.  The  writers  would  also  express  their 
thanks  to  Dr.  H.  McE.  Knower  for  helpful  criticisms  on  Part  I  and  the 
chapter  on  Teratogenesis;  to  Dr.  Edward  Learning  for  making  the  photo- 
graphs reproduced  in  the  text;  to  the  American  Journal  of  Anatomy  for  the 
loan  of  plates;  and  to  Messrs.  William  Wood  &  Company  for  their  uniform 
courtesy  and  kindness. 

FREDERICK  RANDOLPH  BAILEY. 
APRIL  i,   1909.  ADAM  MARION  MILLER. 


CONTENTS, 


PART  I.— GENERAL  DEVELOPMENT. 

CHAPTER  I. 

THE  CELL  AND  CELL  PROLIFERATION i 

The  Cell , i 

Cell  Division 3 

Amitosis 3 

Mitosis 4 

Practical  Suggestions 9 

References  for  Further  Study      9 

CHAPTER  II. 

THE  SEXUAL  ELEMENTS — OVUM  AND  SPERMATOZOON 10 

The  Ovum      10 

The  Spermatozoon 13 

Practical  Suggestions 15 

References  for  Further  Study 16 

CHAPTER  III. 

MATURATION 17 

Maturation  of  the  Ovum  17 

Spermatogenesis 21 

Theoretical  Aspects  of  Reduction 28 

Ovulation  and  Menstruation 3° 

Practical  Suggestions 33 

References  for  Further  Study      34 

CHAPTER  IV. 

FERTILIZATION • 35 

Significance  of  Fertilization      ..,.,...., 4° 

Practical  Suggestions • 41 

References  for  Further  Study      41 

vii 


vill  CONTENTS. 

CHAPTER  V. 

CLEAVAGE  (SEGMENTATION) 42 

Forms  of  Cleavage 42 

Holoblastic  Cleavage 43 

Meroblastic  Cleavage 45 

Some  General  Features  of  Cleavage — Cleavage  in  Mammals 47 

Practical  Suggestions 53 

References  for  Further  Study      54 

CHAPTER  VI. 

GERM  LAYERS 55 

The  Two  Primary  Germ  Layers — Formation  of  the  Gastrula 55 

Gastrulation  in  Amphioxus      55 

Gastrulation  in  Amphibians 56 

Gastrulation  in  Reptiles  and  Birds 61 

Gastrulation  in  Mammals 67 

Formation  of  the  Middle  Germ  Layer — Mesoderm 72 

Mesoderm  Formation  in  Amphioxus      .-  72 

Mesoderm  Formation  in  Amphibians 76 

Mesoderm  Formation  in  Reptiles  and  Birds 78 

Mesoderm  Formation  in  Mammals 85 

The  Germ  Layers  in  Man 89 

Practical  Suggestions 96 

References  for  Further  Study       97 

CHAPTER  VII. 

FOETAL  MEMBRANES 99 

Fcetal  Membranes  in  Birds  and  Reptiles      99 

The  Amnion 99 

The  Yolk  Sac 103 

The  Allantois 106 

The  Chorion  or  Serosa 107 

Fcetal  Membranes  in  Mammals      107 

Amnion,  Chorion,  Yolk  Sac,  Allantois,  Umbilical  Cord 108 

Further  Development  of  the  Chorion m 

The  Fcetal  Membranes  in  Man      115 

The  Amnion 115 

The  Yolk  Sac 117 

The  Allantois      118 

The  Chorion  and  Decidua 119 

The  Decidua  Parietalis 123 

The  Decidua  Capsularis 123 


CONTENTS.  ix 

The  Decidua  Basalis 12^ 

The  Umbilical  Cord      I32 

The  Expulsion  of  the  Placenta  and  Membranes 134 

Anomalies i^ 

Practical  Suggestions ^5 

References  for  Further  Study      136 

CHAPTER  VIII. 

THE  DEVELOPMENT  OF  THE  EXTERNAL  FORM  OF  THE  BODY 137 

Branchial  Arches — Face — Neck      149 

The  Extremities 153 

Age  and  Length  of  Embryos 155 

Normal,  Abnormal  and  Pathological  Embyos      158 

Practical  Suggestions 159 

References  for  Further  Study 161 


PART  II.— ORGANOGENESIS. 

CHAPTER  IX. 

THE  DEVELOPMENT  OF  CONNECTIVE  TISSUES  AND  THE  SKELETAL  SYSTEM    .    .    .165 

Histogenesis 167 

Fibrillar  Forms 170 

Adipose  Tissue 171 

Cartilage      172 

Osseous  Tissue 173 

Intramembranous  Ossification 173 

Intracartilaginous  Ossification 176 

The  Development  of  the  Skeletal  System      182 

The  Axial  Skeleton 182 

The  Notochord 182 

The  Vertebras 183 

The  Ribs 188 

The  Sternum      189 

The  Head  Skeleton 19° 

Ossification  of  the  Chondrocranium 194 

Membrane  Bones  of  the  Skull 196 

Bones  Derived  from  the  Branchial  Arches 198 

The  Appendicular  Skeleton -202 

Development  of  Joints      209 

Anomalies 213 

Practical   Suggestions 2I7 

References  for  Further  Study  , 2I9 


x  CONTENTS. 

CHAPTER  X. 

THE  DEVELOPMENT  OF  THE  VASCULAR  SYSTEM 222 

The  Blood  Vessels  and  Blood 222 

The  Heart 222 

The  Septa 229 

The  Valves 231 

Changes  after  Birth 233 

The  Vessels 235 

Origin      235 

The  Arteries 243 

The  Veins 253 

Histogenesis  of  the  Blood  Cells 270 

The  Lymphatic  System 276 

The  Lymphatic  Vessels 276 

The  Lymph  Glands      279 

The  Spleen 282 

Glomus  Coccygeum 285 

Anomalies 285 

Practical  Suggestions 289 

References  for  Further  Study      291 

CHAPTER  XL 

THE  DEVELOPMENT  OF  THE  MUSCULAR  SYSTEM 293 

The  Skeletal  Musculature 293 

Muscles  of  the  Trunk 295 

Muscles  of  the  Head 300 

Muscles  of  the  Extremities 303 

Histogenesis  of  Striated  Voluntary  Muscle  Tissue 307 

The  Visceral  Musculature 311 

Histogenesis  of  Heart  Muscle      311 

Histogenesis  of  Smooth  Muscle 312 

Anomalies 313 

Practical  Suggestions 314 

References  for  Further  Study      315 

CHAPTER  XII. 

THE  DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGANS     .    .317 

The  Mouth 318 

The  Tongue       321 

The  Teeth * 323 

The  Salivary  Glands '.  , 328 

The  Pharynx .  330 

The  Branchial  Epithelial  Bodies 332 


CONTENTS.  Xi 

The  (Esophagus  and  Stomach ,,5 

The  Intestine  ,og 

Histogenesis  of  the  Gastrointestinal  Tract 343 

The  Development  of  the  Liver 345 

Histogenesis  of  the  Liver oqO 

The  Development  of  the  Pancreas .jcj 

Histogenesis  of  the  Pancreas 354 

Anomalies ^re 

Practical  Suggestions 359 

References  for  Further  Study  360 

CHAPTER  XIII. 

THE  DEVELOPMENT  OF  THE  RESPIRATORY  SYSTEM 362 

The  Larynx 363 

The  Trachea 365 

The  Lungs      366 

Changes  in  the  Lungs  at  Birth 369 

Anomalies 370 

Practical  Suggestions 370 

References  for  Further  Study      371 

CHAPTER  XIV. 

THE  DEVELOPMENT  OF  THE  CGELOM,  THE  PERICARDIUM,  PLEUROPERITONEUM, 

DIAPHRAGM  AND  MESENTERIES 372 

The  Pericardial  Cavity,  Pleural  Cavities  and  Diaphragm 373 

The  Pericardium  and  Pleura 379 

The  Omentum  and  Mesentery 379 

The  Greater  Omentum  and  Omental  Bursa 380 

The  Lesser  Omentum 381 

The  Mesenteries 382 

The  Peritoneum 384 

Anomalies 384 

Practical  Suggestions 385 

References  for  Further  Study 386 

CHAPTER  XV. 

THE  DEVELOPMENT  OF  THE  UROGENITAL  SYSTEM 387 

The  Pronephros 387 

The  Mesonephros      3^9 

The  Kidney  (Metanephros) 394 

The  Ureter,  Renal  Pelvis,  and  Straight  Renal  Tubules 394 

The  Convoluted  Renal  Tubules  and  Glomeruli 396 

The  Renal  Pyramids  and  Renal  Columns 4°° 

Changes  in  the  Position  of  the  Kidneys 402 


Xli  CONTENTS. 


The  Urinary  Bladder,  Urethra,  and  Urogenital  Sinus 403 

The  Genital  Glands      406 

The  Germinal  Epithelium  and  Genital  Ridge 406 

Differentiation  of  the  Genital  Glands, 408 

The  Ovary      -. 409 

The  Testicle 414 

Determination  of  Sex 415 

The  Ducts  of  the   Genital   Glands  and  the  Atrophy  of  the  Meso- 

nephroi 417 

In  the  Female 417 

Oviduct 418 

Uterus  and  Vagina 419 

In  the  Male 420 

Changes  in  the  Positions  of  the  Genital  Glands  and  the  Development 

of  their  Ligaments 421 

Descent  of  the  Testicles 423 

Descent  of  the  Ovaries 426 

The  External  Genital  Organs 427 

The  Development  of  the  Suprarenal  Glands 430 

The  Cortical  Substance 431 

The  Medullary  Substance 431 

Anomalies 433 

Practical  Suggestions 439 

References  for  Further  Study      441 

CHAPTER  XVI. 

THE  DEVELOPMENT  OF  THE  INTEGUMENTARY  SYSTEM 444 

The  Skin 444 

The  Nails 446 

The  Hair 447 

The  Glands  of  the  Skin 449 

The  Mammary  Glands 449 

Anomalies 451 

Practical  Suggestions 453 

References  for  Further  Study      453 

CHAPTER  XVII. 

THE  NERVOUS  SYSTEM 454 

General  Considerations 454 

General  Plan  of  the  Vertebrate  Nervous  System     . 457 

Spinal  Cord  and  Nerves 464 

The  Epichordal  Segmental  Brain  and  Nerves      466 

The  Cerebellum 473 

The  Mid-Brain  Roof 474 

The  Prosencephalon 474 


CONTENTS.  xui 

General  Development  of  the  Human  Nervous  System    During    the    First 

Month      479 

Histogenesis  of  the  Nervous  System 485 

Epithelial  Stage — Cell  Proliferation 486 

Early  Differentiation  of  the  Nerve  Elements 490 

Differentiation  of  the  Peripheral  Neurones  of  the  Cord  and  Epichordal 

Segmental  Brain 493 

Efferent  Peripheral  Neurones      493 

Afferent  Peripheral  and  Sympathetic  Neurones 496 

Development  of  the  Lower  (Intersegmental)  Intermediate  Neurones  .  509 

Further  Differentiation  of  the  Neural  Tube 513 

The  Spinal  Cord 513 

The  Epichordal  Segmental  Brain 519 

The  Cerebellum 532 

Corpora  Quadrigemina 537 

The  Diencephalon 538 

The  Telencephalon  (Rhinencephalon,  Corpora  Striata  and  Pallium)      .  545 

Rhinencephalon 547 

Corpora  Striata  and  Pallium 548 

The  Archipallium      553 

The  Neopallium 559 

Anomalies 5^7 

Practical  Suggestions 568 

References  for  Further  Study 571 

CHAPTER  XVIII. 

THE  ORGANS  OF  SPECIAL  SENSE •    •    •  573 

The  Eye      •    •  573 

The  Lens 575 

The  Optic  Cup      ...  579 

The  Retina 58° 

The  Chorioid  and  Sclera      585 

The  Vitreous 585 

The  Optic  Nerve •    •  586 

The  Ciliary  Body,  Iris,  Cornea,  Anterior  Chamber 587 

The  Eyelids •    -  588 

The  Nose •  589 

The  Ear •  592 

The  Inner  Ear •  592 

The  Acoustic  Nerve      •    •    •  598 

The  Middle  Ear ....  599 

The  Outer  Ear ....  600 

Anomalies 6o1 

Practical  Suggestions "°2 

References  for  Further  Study      6°3 


xiv  CONTENTS. 

CHAPTER  XIX. 

TERATOGENESIS 605 

Malformations  Involving  More  Than  One  Individual 605 

Classification,  Description,  Origin 605 

Symmetrical  Duplicity 606 

Origin  of  Symmetrical  Duplicity 611 

Asymmetrical  Duplicity        612 

Origin  of  Asymmetrical  (Parasitic)  Duplicity 614 

Malformations  Involving  One  Individual 616 

Description,  Origin 616 

Defects  in  the  Region  of  Neural  tube 616 

Origin  of  Malformations  in  the  Region  of  Neural  Tube   ....  619 

Defects  in  Regions  of  the  Face  and  Neck,  and  their  Origin      .    .    .  620 

Defects  in  the  Thoracic  and  Abdominal  Regions,  and  their  Origin  622 

Malformations  of  the  Extremities 622 

Causes  Underlying  the  Origin  of  Monsters 624 

The  Production  of  Duplicate  (Polysomatous)  Monsters    .    .    .    .    .  625 

The  Production  of  Monsters  in  Single  Embryos 626 

The  Significance  of  the  Foregoing  in  Explaining  the  Production 

of  Human  Monsters 627 

References  for  Further  Study      627 

APPENDIX. 

General  Technic 629 

Procuring  and  Handling  Material 629 

Fixation 631 

Hardening 633 

Preservation 633 

Embedding     .    . 633 

Section  Cutting 634 

Staining 635 

Methods  of  Reconstruction      637 

References 638 


INTRODUCTION. 


While  Embryology  as  a  science  is  of  comparatively  recent  date,  recorded 
observations  upon  the  development  of  the  foetus  date  back  as  far  as  1600  when 
Fabricius  ab  Aquapendente  published  an  article  entitled  "  De  Formato  Fcetu." 
Four  years  later  the  same  author  added  some  further  observations  under  the 
title,  "  De  Formatione  Foetus."  Harvey  (1651),  using  a  simple  lens,  studied  and 
described  the  chick  embryo  of  two  days'  incubation.  Harvey's  idea  was  that 
the  ovum  consisted  of  fluid  in  which  'the  embryo  appeared  by  spontaneous 
generation.  Regnier  de  Graaf  (1677)  described  the  ovarian  follicle  (Graafian 
follicle),  and  in  the  same  year  was  announced  the  discovery  by  Von  Loewenhoek 
of  the  spermatozoon.  These  and  other  embryologists  of  this  period  held  what 
is  now  known  as  the  prejormation  theory.  According  to  this  theory,  the  adult 
form  exists  in  miniature  in  the  egg  or  germ,  development  being  merely  an 
enlarging  and  unfolding  of  preformed  parts.  With  the  discovery  of  the 
spermatozoon  the  "  pref ormationists  "  were  divided  into  two  schools,  one  hold- 
ing that  the  ovum  was  the  container  of  the  miniature  individual  (ovists),  the 
other  according  this  function  to  the  spermatozoon  (animalculists).  According 
to  the  ovists,  the  ovum  needed  merely  the  stimulation  of  the  spermatozoon  to 
cause  its  contained  individual  to  undergo  development,  whereas  the  animalcu- 
lists looked  upon  the  spermatozoon  as  the  essential  embryo-container,  the  ovum 
serving  merely  as  a  suitable  food-supply  or  growing-place. 

Nearly  a  hundred  years  of  almost  no  further  progress  in  embryological 
knowledge  came  to  a  close  with  the  publication  of  Wolff's  important  article, 
"Theoria  Generationis,"  in  1759.  Wolff's  theory  was  theory  pure  and  simple, 
with  very  little  basis  on  then  known  facts,  but  it  was  significant  as  being  ap- 
parently the  first  clear  statement  of  the  doctrine  of  epigenesis.  The  two  es- 
sential points  in  Wolff's  theory  were:  (i)  that  the  embryo  was  not  preformed; 
that  is,  did  not  exist  in  miniature  in  the  germ,  but  developed  from  a  more  or  less 
unformed  germ  substance;  (2)  that  union  of  male  and  female  substances  was 
necessary  to  initiate  development.  The  details  of  Wolff's  theory  were  wrong 
in  that  he  looked  upon  the  ovum  as  a  structureless  substance  and  upon  the 
seminal  fluid  and  not  upon  the  spermatozoon  as  the  male  fecundative  agent. 
Dollinger  and  his  two  pupils,  von  Baer  and  Pander,  were  the  next  to  make 
important  contributions  to  Embryology.  Von  Baer's  publication  in  1829  was 
of  extreme  significance  in  the  development  of  embryological  knowledge,  for 

xv 


xvi  INTRODUCTION. 

in  it  we  have  the  first  definite  description  of  the  primary  germ  layers  as  well  as 
the  first  accurate  differentiation  between  the  Graafian  follicle  and  the  ovum. 
It  will  be  remembered  that  the  cell  was  not  as  yet  recognized  as  the  unit  of 
organic  structure.  Only  comparatively  gross  Embryology  was  thus  possible. 
With  the  recognition  of  the  cell  as  the  basis  of  animal  structure  (Schleiden  and 
Schwann,  1839)  the  entire  field  of  histogenesis  was  opened  to  the  embryologist ; 
the  ovurn  became  known  as  a  typical  cell,  while  a  little  later  (Kolliker,  Reichert 
and  others,  about  1840)  was  established  the  function  of  the  spermatozoon 
and  the  fact  that  it  also  was  a  modified  cell  structure.  From  this  time  we 
may  consider  the  two  fundamental  facts  of  Histology  and  of  Embryology, 
respectively,  as  firmly  fixed  beyond  controversy;  for  Histology,  the  fact  that 
the  body  consists  wholly  of  cells  and  cell  derivatives;  for  Embryology,  the 
fact  that  all  of  these  cells  and  cell  derivatives  develop  from  a  single  original 
cell — the  fertilized  ov.um. 

The  adult  body  being  thus  composed  of  an  enormous  number  of  cells,  vary- 
ing in  structure  and  in  function,  forming  the  different  tissues  and  organs,  and 
these  cells  having  all  developed  from  the  single  fertilized  germ  cell,  it  is  the 
province  of  Embryology  to  trace  this  development  from  the  union  of  male 
and  female  germ  cells  to  the  cessation  of  developmental  life. 

While  Embryology  thus  properly  begins  with  the  fertilized  ovum,  that  is, 
with  the  first  cell  of  the  new  individual,  certain  preliminary  considerations  are 
essential  to  the  proper  understanding  of  this  cell  and  its  future  development. 
These  are  the  structure  of  the  ovum  and  of  the  spermatozoon  and  their  de- 
velopment preparatory  to  union.  Also,  as  it  is  with  cells  and  cell  activities 
that  Embryology  has  largely  to  deal,  it  is  necessary  to  consider  the  structure 
of  the  typical  animal  cell  and  the  processes  by  which  cells  undergo  division  or 
proliferation. 

While  the  subject  of  this  work  is  distinctly  human  Embryology,  it  is  neither 
possible  nor  advisable  to  confine  our  study  wholly  to  human  material.  It  is  not 
possible,  for  the  reason  that  material  for  the  study  of  the  earliest  stages  in  the 
human  embryo  (first  12  days)  is  entirely  wanting,  while  human  embryos  of 
under  20  days  are  extremely  rare.  Again,  even  later  stages  in  human  develop- 
ment are  often  best  understood  by  comparison  with  similar  stages  in  lower 
forms.  For  practical  study  by  the  student,  human  material  for  all  even  of 
the  later  stages  is  rarely  available,  so  that  recourse  must  frequently  be  had  to 
material  from  lower  animals.  Such  study  is,  however,  usually  thoroughly 
satisfactory  if  the  student  has  sufficient  knowledge  of  comparative  anatomy,  and 
the  deductions  regarding  human  development,  from  the  study  of  development 
in  lower  forms,  are  rarely  in  error. 


PART  I. 

GENERAL  DEVELOPMENT. 


A  TEXT-BOOK  OF  EMBRYOLOGY 


CHAPTER  I. 

THE  CELL  AND  CELL  PROLIFERATION. 
THE  CELL. 

The  Typical  Animal  Cell  (Fig.  i)  is  a  small  definitely  restricted  mass  of 
protoplasm.  It  contains  or  has  at  some  period  of  its  development  contained 
two  specially  differentiated  bodies,  the  nucleus  and  the  centrosome.  It  may  be 
limited  by  a  more  or  less  definite  cell  membrane. 

Of  the  ultimate  structure  of  living  protoplasm  our  knowledge  is  extremely 
small.  It  is  of  an  albuminous  nature,  coagulated  by  heat  and  by  many  chemical 
reagents.  It  varies  both  in  structure  and  in  chemical  composition  in  different 
cells  and  is  probably  best  considered,  not  as  a  definite  structure  either  chemically 
or  morphologically,  but  as  the  material  basis  of  life  activities.  Protoplasm  carf 
usually  be  resolved  into  a  formed  part,  spongioplasm,  which  takes  the  form  of  a 
reticulum,  a  feltwork,  or  fibrillse,  and  an  unformed  homogeneous  element, 
hyaloplasm,  which  fills  in  the  meshes  of  the  reticulum  or  forms  the  perifibrillar 
substance.  Various  protoplasmic  inclusions  are  frequently  found  in  cells.  To 
these  the  term  metaplasm  (paraplasm,  deutoplasm)  has  been  applied.  Among 
them  may  be  mentioned  plastids,  fat  droplets,  pigment  granules  and  various 
excretory  and  secretory  substances. 

The  NUCLEUS  is  usually  separated  from  the  rest  of  the  protoplasm  by  a 
nuclear  membrane.  Within  the  nucleus  the  nuclear  membrane  is  continuous 
with  a  nuclear  reticulum  which  consists  of  two  parts :  a  chromatic  part — chroma- 
tin,  and  an  achromatic  part — linin.  At  nodal  points  of  the  network  there  are 
frequently  considerable  accumulations  of  chromatin  to  form  net  knots  (false 
nucleoli  or  karyosomes).  Filling  the  meshes  of  the  nuclear  reticulum  is  a  fluid 
or  semifluid  substance,  the  nudeoplasm  or  karyoplasm.  The  structure  of  the 
nucleus  is  thus  seen  to  correspond  closely  to  the  structure  of  the  surrounding 
protoplasm.  This  is  especially  evident  in  those  cells  in  which  there  is  no 
limiting  nuclear  membrane,  the  nuclear  reticulum  and  the  cytoreticulum  being 
continuous,  the  nucleoplasm  and  cytoplasm  mingling.  This  condition,  true 


TEXT-BOOK  OF  EMBRYOLOGY. 


only  for  some  resting  cells,  is  always  present  in  cells  which  are  undergoing 
mitotic  division. 

In  addition  to  the  net  knots  are  the  true  nucleoli  or  plasmosomes.  These  are 
spheroidal  bodies  which  lie  free  in  the  meshes  of  the  nuclear  reticulum.  They 
vary  in  number  in  different  cells  and  sometimes  in  the  same  cell  in  different 
conditions  of  activity.  They  stain  intensely  with  basic  dyes.  The  function 
of  the  nucleolus  is  not  known.  It  has  been  regarded  by  some  as  material  in 
process  of  constructive  metabolism,  by  others  as  a  waste  product. 

The  nucleus  is  typically  spherical.  Its  shape  may  or  may  not  be  modified 
by  the  shape  of  the  cell  body.  Nuclei  may  assume  very  irregular  shapes,  as  in 
poly morphonucl ear  leucocytes,  or  they  may  be  lobulated,  as  in  some  of  the 


Cell  membrane   " 

Metaplasm  1    <;' 
granules    J 

Karyosome  or  1     • 
net  knot       j 


Hyaloplasm 
Spongioplasm 

Linin  network 
Nucleoplasm 


Aster  (attraction-sphere) 
Centriole 


~~~-~*    Plastids  (metaplasm) 


Chromatin  network 
Nuclear  membrane 


""    Nucleolus 


Vacuole 


FIG.  i. — Diagram  of  a  typical  cell.     Bailey. 

large  cells  of  bone  marrow;  or  a  cell  may  have  a  number  of  nuclei.  The  shape 
of  the  nucleus  may  vary  considerably  within  comparatively  short  periods  of  time. 
Such  nuclei  have  been  described  as  having  amoeboid  movement.  The  size 
of  the  nucleus  also  appears  to  be  independent  of  the  size  of  the  cell  body,  some 
large  cells  having  small  nuclei,  while  some  small  cells  are  almost  completely 
filled  by  their  nuclei.  The  nucleus  tends  to  lie  near  the  center  of  the  cell,  yet 
may  be  eccentric  to  any  degree  and  appears  to  be  suspended  in  the  cytoplasm 
in  such  a  way  that  its  location  within  the  cell  may  change.  In  some  of  the  lowest 
forms  no  true  nuclear  structure  exists,  scattered  granules  of  chromatin  consti- 
tuting the  rudimentary  nucleus,  generally  called  a  diffuse  nucleus. 

As  the  nucleus  is  an  essential  element  in  all  reproduction,  it  follows  that  all 
cells  have  been  nucleated  at  some  time  in  their  developmental  history,  and  that 
the  adult  nonnucleated  condition  of  some  cells  (e.g.,  respiratory  epithelium) 
is  indicative  of  their  having  passed  beyond  the  age  of  reproductive  power.  If 
the  nucleus  be  removed  from  a  living  cell,  the  cytoplasm  does  not  necessarily 


THE  CELL  AND  CELL  PROLIFERATION.  3 

die,  but  may  live  for  some  time  and  show  active  motile  powers.  Such  a  de- 
nucleated  cell  has,  however,  lost  two  of  its  most  important  functions:  (i)  its 
power  of  constructive  metabolism;  that  is,  of  taking  up  nutritive  material  from 
without  and  building  this  up  into  its  own  peculiar  structure — the  power  of 
repair;  and  (2)  the  power  of  reproduction.  For  these  reasons  the  nucleus  has 
been  considered  as  especially  presiding  over  these  two  cell  functions. 

The  CENTROSOME  is  a  structure  found  in  the  cytoplasm  near  the  nucleus, 
less  commonly  within  the  nucleus.  It  consists  typically  of  a  minute  central 
granule,  the  centriole,  a  relatively  clear  surrounding  area,  the  centrosphere,  and, 
radiating  from  this,  the  delicate  rays  which  constitute  the  aster  or  attraction 
sphere  (Fig.  i).  On  account  of  the  behavior  of  the  centrosome  in  relation  to 
cell  division,  it  is  usually  looked  upon  as  the  dynamic  center  of  the  cell. 

In  the  simplest  forms  of  animal  life  a  single  cell,  such  as  has  been  described 
above,  constitutes  the  entire  individual,  and  as  such  is  capable  of  performing 
the  functions  which  are  recognized  as  characteristic  of  living  organisms — metab- 
olism, irritability,  motion,  reproduction  and  special  functions.  The  develop- 
mental history  of  such  an  individual  is  extremely  simple.  The  nucleus  under- 
goes division  and  this  is  accompanied  or  followed  by  division  of  the  cytoplasm. 
The  single  cell  thus  becomes  two  cells,  similar  in  all  respects  to  the  parent  cell. 

In  all  higher,  that  is  multicellular  animals,  however,  the  different  functions 
are  distributed  specifically  to  different  cells  and  these  cells  are  specifically 
differentiated  morphologically  for  the  performance  of  these  different  functions. 
There  is,  therefore,  not  the  simple  division  of  a  parent  cell  to  form  two  similar 
daughter  cells,  each  constituting  an  individual,  but  a  differentiation  from  the 
single  original  germ  cell,  the  fertilized  ovum,  of  many  different  kinds  of  cells, 
and  their  specialization  to  form  the  various  tissues  and  organs  which  constitute 
the  adult  body. 

CELL  DIVISION. 

In  the  development  of  the  embryo,  cell  division  of  course  succeeds  fertiliza- 
tion. A  proper  understanding,  however,  of  the  changes  which  take  place  in 
the  ovum  and  in  the  spermatozoon  previous  to  fertilization  requires  the  con- 
sideration of  cell  division  at  this  point. 

Two  types  of  cell  division  are  recognized :  (i)  direct  cell  division  or  amitosis 
and  (2)  indirect  cell  division  or  mitosis. 

(i)  Amitosis  (Fig.  2). — In  this  form  of  cell  division  there  is  no  formation  of 
spindleorof  chromosomes  (see  Mitosis,  p.  4),  the  nucleus  retaining  itsreticular 
structure  during  division.  There  is  first  a  constriction  of  the  nucleus,  followed 
by  complete  division  into  two  daughter  nuclei.  During  the  division  of  the 
nucleus  a  constriction  appears  in  the  cytoplasm.  This  increases  until  the 
cytoplasm  is  divided  into  two  separate  masses  (daughter  cells),  each  containing 


TEXT-BOOK  OF  EMBRYOLOGY. 


a  nucleus.  This  form  of  cell  division,  which  was  considered  by  Remak  and  his 
associates  (1855-1858)  as  the  only  method  by  which  cells  proliferated,  is  now 
known  to  be  of  rare  occurrence.  Flemming  goes  so  far  as  to  state  that  in  the 
higher  animals  amitosis  never  occurs  as  a  normal  physiological  process  in  ac- 
tively dividing  cells,  but  is  rather  to  be  considered  as  a  degeneration  phenomenon 
occurring  in  cells  wrhose  reproductive  powers  are  on  the  wane.  It  frequently 
results  in  nuclear  division  only,  the  cytoplasm  remaining  undivided,  thus  giving 
rise  to  multinuclear  cells.  It  is  a  common  method  of  cell  division  in  the 
Protozoa. 

(2)  Mitosis. — In  this  form  of  cell  division  the  cell  passes  through  a  series 
of  complicated  changes.  These  changes  occur  as  a  continuous  process,  but 

for  clearness  of  description  it  is  convenient 
to  arbitrarily  subdivide  the  process  into  a 
number  of  phases.  These  are  known  as  the 
prophase,  the  metaphase,  the  anaphase,  and 
the  telophase.  Of  these  the  prophase  in- 
cludes the  changes  preparatory  to  division 
of  the  nucleus;  the  metaphase,  the  actual 
separation  of  the  nuclear  elements;  the 
anaphase,  their  arrangement  to  form  the  two 
daughter  nuclei;  the  telophase,  the  division 
of  the  cytoplasm  to  form  two  daughter  cells 
and  the  reconstruction  of  the  two  daughter 
nuclei. 

PROPHASE  (Fig.  3). — In  actively  divid- 

FIG.  2. — Epithelial  cells  from  ovary  of   ing  cells  the  centrosome,  or,  more  specific- 
cockroach,  showing   nuclei  dividing  ami-       11,1  .   •    i  i       j      i  ,      ,-.->• 

toticaiiy.    Wheeler.  alI7>  the  centriole,  may  be  double  (Fig.  3, 

A),  having  undergone  division  as  early,  fre- 
quently, as  the  anaphase  of  the  preceding  division  (p.  6).  Each  centriole 
is  surrounded  by  a  clear  area,  the  centrosphere,  from  which  radiate  the 
delicate  astral  rays,  the  whole  being  known  as  the  attraction  sphere  (Fig.  3, 
B,  C,  D).  Connecting  the  two  centrosomes  are  other  delicate  fibrils  forming  a 
structure  known  as  the  central  or  achromatic  spindle  (Fig.  3,  B,  better  developed 
in  C  and  D).  The  two  centrioles  with  their  surrounding  centrospheres,  astral 
rays  and  connecting  spindle,  constitute  the  amphiaster.  If  the  resting  cell 
contains  only  one  centriole,  division  of  the  centriole  with  formation  of  the 
amphiaster  is  usually  the  first  phenomenon  of  mitosis,  the  connecting  central 
spindle  fibers  appearing  as  the  centrioles  move  apart. 

During  or  following  the  formation  of  the  amphiaster,  important  changes 
occur  in  the  nucleus.  It  increases  somewhat  in  size  and  the  reticulum  charac- 
teristic of  the  resting  nucleus  becomes  converted  into  a  single  long  thread 


THE   CELL  AND   CELL  PROLIFERATION. 


(spireme  thread)  arranged  in  a  closed  skein — dosed  spireme  (Fig.  3,  B).  This 
soon  becomes  more  loosely  arranged,  the  thread  at  the  same  time  becoming 
shorter  and  thicker  and  frequently  broken,  forming  the  open  spireme.  During 
the  formation  of  the  spireme  the  nucleolus  and  nuclear  membrane  usually 
disappear,  the  nucleoplasm  thus  becoming  continuous  with  the  cytoplasm. 
The  spireme  now  lies  with  the  amphiaster  in  the  general  cell  protoplasm. 
The  morphological  change  from  reticulum  to  spireme  is  apparently  accom- 


FIG.  3. — Diagrams  of  successive  stages  of  mitosis.     Wilson. 

A,  Resting  cell  with  reticular  nucleus  and  true  nucleus;  c,  two  centrioles — the  single  preceding 

one  having  divided  in  anticipation  of  the  division  of  nucleus  and  cell  body. 

B,  Early    prophase.     Chromatin    forming   a    continuous   thread — closed    spireme;  nucleolus    still 

present;  a,  centrioles  surrounded  by  astral  rays  and  connected  by  achromatic  spindle. 

C,  Later  prophase.     Spireme  has   segmented   to  form  chromosomes;   astral  rays  and  achromatic 

spindle  larger  and  more  distinct;  nuclear  membrane  less  distinct. 

D,  End  of  prophase;  ep,  chromosomes  arranged  in  equatorial  plane  of  spindle. 

panied  by  changes  of  a  chemical  nature,  as  the  spireme  thread  stains  much 
more  intensely  than  do  the  strands  of  the  reticulum. 

The  next  step  is  the  transverse  division  of  the  spireme  thread  into  a  number 
of  segments  (Fig.  3,  C).  These  are  usually  at  first  rod-shaped,  and  are 
known  as  chromosomes.  They  may  remain  rod-shaped  or  the  rods  may 
become  bent  to  form  U's  or  Vs.  Some  chromosomes  are  spheroidal.  The 
most  remarkable  feature  of  the  breaking  up  of  the  spireme  thread  to  form 


6  TEXT-BOOK  OF  EMBRYOLOGY. 

chromosomes  is  that  the  number  of  segments  into  which  the  thread  divides, 
while  differing  for  different  species  of  plants  and  animals,  is  fixed  and  definite 
for  each  particular  species.  For  example,  in  Ascaris  megalocephala — a  very 
convenient  type  for  study  on  account  of  its  simplicity — the  number  of  chro- 
mosomes is  4,  in  the  mouse  24.  In  man  the  number  is  not  known  with 
certainty;  by  some  it  is  estimated  at  16,  by  others  at  24. 

There  are  thus  at  this  stage  present  in  the  cytoplasm,  two  distinct  though 
closely  related  structures — the  amphiaster  and  the  chromosomes.  These 
together  constitute  the  mitotic  figure.  As  the  chromosomes  form  they  become 
arranged  in  the  equator  of  the  central  spindle,  along  what  is  known  as  the 
equatorial  plane  (Fig.  3,  D).  When,  as  is  frequently  the  case,  the  chromosomes 
are  U-shaped,  the  closed  ends  of  the  loops  lie  toward  the  center,  the  open  ends 
radiating.  Three  sets  of  fibers  can  now  be  distinguished  in  connection  with  the 
centrosomes  (Fig.  3,  C,  D) :  (i)  the  fibers  of  the  central  spindle  connecting 
the  two  centrosomes;  (2)  the  polar  rays  which  radiate  from  the  centriole 
toward  the  periphery  of  the  cell;  (3)  the  mantle  fibers  which  pass  from  the 
centrosomes  to  the  chromosomes. 

The  mitotic  figure  is  at  this  stage  knowrn  as  the  monaster,  and  its  complete 
formation  marks  the  end  of  the  prophase. 

METAPHASE. — The  essential  feature  of  the  metaphase  is  the  longitudinal 
splitting  of  each  chromosome  into  exactly  similar  halves  (Fig.  4,  E),  each  half 
containing  an  equal  amount  of  the  chromatin  of  the  parent  chromosome.  In 
the  case  of  U-  or  V-shaped  chromosomes,  the  splitting  begins  at  the  crown 
and  extends  to  the  open  ends.  The  latter  often  remain  united  for  a  time, 
giving  the  appearance  of  rings  or  loops.  The  significance  of  this  equal  longi- 
tudinal splitting  of  the  chromosomes  is  apparent  when  one  considers  that 
through  this  means  an  exactly  equal  part  of  each  chromosome  and  thus  exactly 
equivalent  parts  of  the  chromatin  of  the  parent  nucleus  are  distributed  to  the 
nucleus  of  each  daughter  cell. 

ANAPHASE. — Actual  division  of  the  chromosomes  having  taken  place,  the 
next  step  is  their  separation  to  form  the  daughter  nuclei.  In  separating,  the 
daughter  chromosomes  pass  along  the  fibers  of  the  central  spindle  (Fig.  4,  F), 
apparently  under  the  guidance  of  the  mantle  fibers,  each  group  towrard  its 
respective  centrosome,  around  which  the  chromosomes  finally  become  arranged 
(Fig.  4,  G),  thus  forming  two  daughter  stars.  The  mitotic  figure  is  now 
known  as  the  diaster.  In  actively  dividing  cells  it  is  common  for  the  centriole 
to  undergo  division  at  this  stage,  thus  making  four  centrioles  in  the  cell. 
(Fig.  4,  F,  G.) 

TELOPHASE  (Fig.  4,  H). — This  is  marked  by  division  of  the  cytoplasm, 
usually  in  the  equatorial  plane  of  the  achromatic  spindle,  and  the  reconstruction 
of  the  two  daughter  nuclei.  Each  new  cell  now  contains  a  nucleus,  a  centrosome 


THE   CELL  AND   CELL  PROLIFERATION. 


with  its  aster  (or  two  centrioles  with  asters)  and  one-half  the  achromatic 
spindle.  The  resting  nucleus  is  formed  by  a  reverse  of  the  series  of  changes 
described  as  occurring  in  the  prophase,  the  chromosomes  uniting  end  to  end  to 
form  a  skein  or  spireme,  lateral  buds  appearing  which  anastomose,  thus  giving 
rise  to  the  reticulum  of  the  resting  nucleus.  The  nucleolus  reappears  as 
mysteriously  as  it  disappeared  during  the  prophase  and  the  nuclear  membrane 
is  reformed. 


FIG.  4. — Diagrams  of  successive  stages  of  mitosis.     Wilson. 

E,  Metaphase.     Longitudinal    splitting    of    chromosomes    to    form   daughter  chromosomes,   ep; 

n,  cast-off  nucleolus. 

F,  Anaphase.     Daughter  chromosomes  passing  along  fibers  of  achromatic, spindle  toward  centro- 

somes;   centrioles  again  divided;  if,  interzonal  fibers  of  central  spindle. 
C,  Late  anaphase.     Chromosomes  at  ends  of  spindle;  spindle  fibers  less  distinct;  thickenings  of 

fibers    in    equatorial    plane  indicate  beginning  of  cytoplasmic  plate;  cell  body  beginning  to 

divide;  nucleolus  has  disappeared. 
H,  Telophase.     Cell   body  divided;   chromatic  substance  in  each  daughter  nucleus  as  in  resting 

stage;  nuclear  membrane  and  nucleolus  has  reappeared  in  each  daughter  cell. 

It  is  to  be  noted  that  the  number  of  chromosomes  which  enter  into  the  forma- 
tion of  the  chromatic  reticulum  of  the  resting  nucleus  is  the  same  as  the  number 
of  chromosomes  derived  from  that  nuclear  reticulum  when  the  cell  prepares  for 
mitotic  division.  It  is  thus  possible  that  the  chromosomes  maintain  their 
individuality  even  during  the  resting  stage. 

In  plant  mitosis  the  central  spindle  fibers  show  minute  chromatic  thicken- 


8  TEXT-BOOK  OF  EMBRYOLOGY. 

ings  along  the  plane  of  future  division  of  the  cell,  forming  what  is  known  as  the 
mid-body  or  cell-plate.  This  splits  into  two  layers,  between  which  the  division 
of  the  cell  takes  place.  The  formation  of  a  distinct  cell-plate  in  animal 
mitosis  is  rare.  In  place  of  this  there  is  a  modification  of  the  cytoplasm  along 
the  line  of  future  division,  sometimes  called  the  cytoplasmic  plate. 

As  to  what  may  be  called  the  dynamics  of  mitosis,  there  has  been  much 
controversy,  but  comparatively  little  has  been  definitely  settled. 

It  would  appear  that  in  most  cases  the  centrosome  is  the  active  agent  in 
initiating,  and  possibly  in  further  controlling  the  mitotic  process.  Boveri, 
for  this  reason,  refers  to  the  centrosome  as  the  "dynamic  center"  of  the  cell. 
The  centriole  first  divides  into  two,  around  each  of  which  an  astral  system  of 
fibers  is  formed.  The  origin  of  these  fibers  appears  to  differ  in  different  cells. 
Thus,  in  some  cases — Infusoria,  for  example — the  centrosome  lies  within  the 
nucleus  and  the  entire  mitotic  figure  apparently  develops  from  nuclear  struc- 
tures. In  some  of  the  higher  plants  both  central  spindle  fibers  and  asters 
are  formed  from  the  spongioplasm.  In  still  other  cases — for  example,  the  eggs 
of  Echinoderms — part  of  the  figure  (the  asters)  is  developed  from  the  cytoplasm, 
while  the  fibers  of  the  central  spindle  are  of  nuclear  origin. 

It  must,  however,  be  admitted  that  centrosome  activity  is  not  absolutely 
essential  to  cell  division,  for  there  are  cases  in  which  division  of  the  chromo- 
somes occurs  without  division  of  the  centrosome,  while  in  the  higher  plants 
mitosis  occurs,  although  no  centrosome  can  be  distinguished  at  any  stage  of 
the  process. 

The  behavior  of  the  centrosome  before,  during  and  after  mitosis  varies  in 
different  cells.  In  some  cells  the  centriole  is  apparently  an  integral  part  of 
the  cell,  persisting  throughout  the  resting  stage.  With  it  may  remain  more 
or  less  of  the  aster,  the  whole  constituting  the  already  mentioned  attraction 
sphere.  In  other  cells — for  example,  mature  egg  cells — the  centriole  with 
its  fibrils  apparently  entirely  disappears  during  the  resting  stage. 

In  regard  to  the  origin  of  the  chromatic  portion  of  the  mitotic  figure,  no 
difference  of  opinion  exists,  so  evidently  does  it  arise,  as  already  noted,  from  the 
chromatic  portion  of  the  nuclear  reticulum.  Its  destination  in  the  nuclear 
reticulum  of  the  daughter  cells  is  equally  well  established.  The  details  of  the 
formation  of  the  chromosomes  vary.  Thus  in  some  cases  there  is  no  single 
spireme  thread,  the  spireme  being  segmented  from  its  formation,  each  segment 
of  course  corresponding  with  a  future  chromosome.  In  other  cases  no  spireme 
whatever  is  formed,  the  chromosomes  taking  origin  directly  from  the  nuclear 
reticulum.  In  still  other  cases  the  spireme  while  yet  a  single  thread  splits 
longitudinally  so  that  there  are  two  threads  present,  the  transverse  divisions 
into  chromosomes  taking  place  subsequently. 

As  to  the  time  required  for  the  mitotic  process,  considerable  variation  exists 


THE   CELL  AND   CELL  PROLIFERATION.  9 

The  process  usually  requires  from  one-half  to  three-quarters  of  an  hour,  but 
may  extend  over  from  two  to  three  hours. 

Mitosis  is  naturally  most  active  wherever  active  growth  of  tissue  is  taking 
place — for  example,  in  embryonic  tissues,  in  granulation  tissue,  in  the  healing 
of  wounds,  in  rapidly  growing  tumors  (usually  an  evidence  of  malignancy). 
The  earlier  generations  of  cells  derived  from  the  fertilized  ovum  are  indifferent 
cells  in  the  sense  that  they  are  capable  of  development  into  any  type  of  tissue 
cells.  As  differentiation  takes  place,  the  cells  assume  more  definite  and  fixed 
types.  With  differentiation,  mitosis  becomes  less  and  less  active  and  cells 
become  incapable  of  producing  cells  of  any  type  other  than  their  own.  Finally, 
the  most  highly  differentiated  (specialized)  cells — for  example,  muscle  cells  and 
nerve  cells — lose  entirely  their  powers  of  reproduction,  and  if  destroyed  are  not 
replaced  by  new  cells  of  the  same  type. 

What  is  known  as  multipolar  or  pluripolar  mitosis  occurs  in  some  of  the 
higher  plants,  less  commonly  in  the  rapidly  growing  connective  tissue  of  healing 
wounds  and  in  cancer  cells.  Such  atypical  mitosis  has  also  been  artificially 
induced  in  rapidly  dividing  cells  by  the  injection  of  chemical  substances  into  the 
tissues.  In  multipolar  mitosis  the  centrosome  divides  into  more  than  two 
daughter  centrosomes  and  not  infrequently  results  in  an  unequal  distribution  of 
chromatin  to  the  daughter  cells. 

PRACTICAL  SUGGESTIONS. 

The  larval  salamander  and  newt  are  classical  subjects  for  the  study  of  cell  division. 
The  small  larvae  are  fixed  in  Flemming's  fluid,  cut  into  thin  sections  in  either  celloidin  or  par- 
affin and  stained  with  Heidenhain's  haematoxylin  (see  Appendix).  Mitotic  figures  may  be 
found  in  almost  any  of  the  tissues. 

Certain  vegetable  tissues,  such  as  magnolia  buds  or  the  root -tips  of  rapidly  growing 
onions,  also  afford  excellent  material  for  the  study  of  mitosis.  The  technic  is  the  same  as 
for  animal  tissues. 

References  for  Further  Study. 

COXKLIX,  E.  G.:  Karyokinesis  and  Cytokinesis.  Jour.  Acad.  Nat.  Sci.  0}  Philadel- 
phia, Vol.  XII,  1902. 

HERTWIG,  O.:  Die  Zelle  und  die  Gewebe.     1898. 

LILLIE,  F.  R.:  A  Contribution  towards  an  Experimental  Analysis  of  the  Karyokinetic 
Figure.  Science,  New  Series,  Vol.  XXVII,  1908. 

WILSOX,  E.  B.:  The  Cell  in  Development  and  Inheritance.     2d  Ed.,  1900. 


CHAPTER  II. 
THE  SEXUAL  ELEMENTS— OVUM  AND  SPERMATOZOON. 

In  practically  the  whole  animal  kingdom  and  without  exception  in  the  entire 
vertebrate  series  the  development  of  a  new  being  can  take  place  only  when 
reproductive  elements,  produced  by  two  sexually  different  individuals,  are 
brought  into  union  at  the  proper  time  as  the  result  of  the  procreative  act. 
These  elements  are,  on  the  one  hand,  the  egg  or  ovum,  which  is  produced  by  the 
female,  and,  on  the  other  hand,  the  seminal  filament  or  spermatozoon  produced 
by  the  male. 

To  a  student  of  histology  it  is  a  matter  of  knowledge  that  the  ovum  and 
spermatozoon  are  histological  units  or  cells.  It  is  a  familiar  fact,  too,  that 
both  are  produced  in  special  glandular  organs — the  ovum  in  the  ovary  of  the 
female  and  the  spermatozoon  in  the  testis  of  the  male.  Furthermore,  it  is 
known  that  during  sexual  maturity  they  detach  themselves  from  the  sexual 
organs  at  definite  times.  They  then  form  under  suitable  conditions,  among 
which  the  union  of  the  two  sex  cells  is  the  most  important,  the  starting  point  of 
a  new  organism.  As  a  necessary  preliminary  to  the  understanding  of  the 
development  which  follows  the  union  of  the  two  sex  cells,  a  brief  consideration 
of  the  structural  and  to  a  certain  extent  of  the  physiological  peculiarities  of 
these  cells  is  essential. 

THE   OVUM. 

The  ovum  or  egg  cell  is  a  cell  specially  organized  for  the  perpetuation  of  the 
species.  It  possesses  those  extraordinary  peculiarities  of  growth  and  differ- 
entiation possessed  by  no  other  cell,  which  enable  it  to  give  rise  directly  to  a 
new  organism  with  all  the  characteristics  of  the  species.  Among  Vertebrates, 
however,  the  process  of  development  is  made  possible  only  by  union  with  the 
male  sexual  element — the  spermatozoon.  It  should  be  stated,  moreover,  that 
the  ovum  as  seen  in  a  Graafian  follicle  in  the  ovary  is  not  a  true  sexual  element, 
not  having  undergone  certain  processes  which  eliminate  part  of  its  chromatic 
substance  and  put  it  on  a  par  with  the  spermatozoon  as  a  mature  sexual  ele- 
ment (see  page  27).  The  large  egg  cell  in  the  ovary  is  properly  called  a 
primary  oocyte. 

With  the  exception  of  some  neurones,  the  human  ovum  (Fig.  5)  is  the 
largest  cell  in  the  body.  It  is  spherical  in  shape,  measuring  from  0.15  mm.  to 
0.2  mm.  in  diameter,  contains  a  large  spherical  nucleus  and  is  surrounded  by  a 
relatively  thick,  transparent  membrane.  As  seen  in  section  in  the  ovary  it  has 

10 


THE   SEXUAL  ELEMENTS — OVUM  AND   SPERMATOZOON. 


11 


essentially  the  structure  of  a  typical  cell.  Around  the  ovum  and  separated 
from  it  by  a  narrow  cleft — the  perivitelline  space— is  the  zona  pellucid  a,  a  rather 
thick,  highly  refractive  membrane  which  shows  radial  striations.  These 
striations  are  probably  due  to  the  presence  of  minute  canals  which  penetrate  the 
zona.  It  has  been  suggested  that  these  canals  serve  for  the  passage  of  nutri- 
ment to  the  ovum.  Immediately  outside  of  the  zona  pellucida  the  epithelial 
cells  of  the  Graafian  follicle  are  arranged  radially  in  one  or  two  layers.  These 


nzss: 


Corona 
radiata 


Yolk 

granules. 


Zona 
pellucida 


FIG.  5. — From  a  section  of  the  ovary  of  a  12  year  old  girl.  The  primary  oocyte  lies  in  a  large 
mature  Graafian  follicle  and  is  surrounded  by  the  cells  of  the  "germ  hill"  (the  inner  edge  of  which 
is  shown  in  the  upper  left-hand  corner  of  the  figure).  Photograph. 

constitute  the  corona  radiata  (Fig.  5).  Some  investigators  have  described  a 
thin,  delicate  mtelline  membrane  between  the  perivitelline  space  and  the  ovum. 
Others  have  failed  to  observe  this. 

The  egg  protoplasm,  originally  called  the  vitellus,  differs  from  the  pro- 
toplasm of  most  cells  in  that  it  appears  somewhat  more  opaque  and  coarsely 
granular.  This  appearance  is  due  to  the  fact  that  the  ovum  stores  up  within 
itself  food  stuffs.  These  consist  of  fatty  and  albuminous  substances  which  are 


12 


TEXT-BOOK  OF  EMBRYOLOGY. 


later  utilized  in  the  growth  and  increase  of  the  embryonic  cells.  The  food 
granules — deutoplasm — are  suspended  in  the  cytoplasm.  The  distribution, 
however,  of  these  granules  in  the  human  ovum  is  not  uniform;  a  mass  of  them 
being  found  in  the  center  of  the  cell  surrounding  the  nucleus,  while  an  almost 
clear  zone  of  cytoplasm  forms  the  periphery  of  the  cell. 

The  nucleus  of  the  ovum  occupies  a  position  near  the  center  within  the 
deutoplasm  mass,  though  in  the  ovum  of  a  mature  Graafian  follicle  it  is  almost 
invariably  slightly  eccentric.  It  is  large  proportionately  as  the  ovum  is  large. 
Its  structure  does  not  differ  essentially  from  that  of  any  other  nucleus.  There 
is  a  distinct  nuclear  membrane  enclosing  the  usual  nuclear  structures — the 
nuclear  liquid,  the  network  of  chromatin,  the  achromatic  network  and  a  single 

nucleolus  or  germinal  spot  (p.  2,  Fig.  i).  In 
a  fresh  human  ovum  amoeboid  movements 
have  been  observed  in  the  nucleolus.  The 
significance  of  the  nucleolus  is  as  little  known 
as  in  any  other  cell. 

A  centrosome,  though  it  may  be  present, 
has  not  been  observed  in  the  human  ovum. 

The  amount  and  distribution  of  the  yolk 
granules  have  an  important  bearing  upon  the 
changes  which  take  place  in  the  egg  subse- 
quent to  fertilization  and  have  led  to  the 
classification  of  eggs  as  alecithal,  telolecithal 
and  centrolecithal.  Alecithal  eggs  (Fig.  5)  are 
those  in  which  the  yolk  granules  are  fairly 
evenly  distributed  throughout  the  cytoplasm 
( Amphioxus,  most  Mammals,  including  man). 
Telolecithal  eggs  (Figs.  6  and  7)  are  those  in 
which  the  yolk  is  in  excess  at  one  pole,  the 

cytoplasm  at  the  opposite  pole  (Amphibians,  Reptiles,  Birds).  Centrolecithal 
eggs  are  those  in  which  a  central  yolk  mass  is  surrounded  by  a  compara- 
tively thin  layer  of  cytoplasm  (Arthropods).  (For  further  description  see 
Cleavage,  page  42.) 

Telolecithal  ova  show  a  condition  known  as  polar  differentiation.  By 
polar  differentiation  is  meant  the  more  or  less  complete  separation  of  cytoplasm 
and  deutoplasm,  so  that  the  cytoplasm  is  present  in  excess  at  one  pole  of  the  egg 
and  the  deutoplasm  in  excess  at  the  opposite  pole.  The  frog's  egg  is  a  familiar 
example  of  this  differentiation,  the  dark  side  of  the  egg  indicating  an  excess  of 
cytoplasm.  Inasmuch  as  deutoplasm  is  generally  heavier  than  cytoplasm,  an 
egg  with  polar  differentiation,  if  left  free  to  revolve,  as  in  water,  will  assume  a 
definite  position  with  the  protoplasmic  or  animal  pole  above  and  the  deuto- 


FIG.  6. — Semidiagrammatic  representa- 
tion of  ovum  of  frog  (Rana  sylvatica). 
The  dark  shading  represents  the  cyto- 
plasmic  pole,  the  light  shading  immedi- 
ately below  represents  the  deutoplasmic 
pole.  The  light  shading  around  the 
ovum  represents  the  gelatinous  sub- 
stance (secondary  egg  membrane). 


THE   SEXUAL  ELEMENTS — OVUM  AND   SPERMATOZOON. 


13 


plasmic  or  vegetative  pole  below.     An  exception  to  this  is  found,  however,  in 
the  pelagic  teleost  eggs,  which  float  with  the  deutoplasmic  pole  upward. 

In  the  hen's  egg  the  cytoplasm  and  deutoplasm  are  distinct  and  separate 
with  no  mingling  of  the  two  substances  (Fig.  7).  While  still  in  the  ovary,  the 
egg  consists  of  the  yellow  yolk  in  the  form  of  an  enormously  large  cell  sur- 
rounded by  the  zona  pellucida,  upon  which  lies  a  small  white  spot,  the  so- 
called  germinal  disk.  The  disk  is  3  or  4  mm.  in  diameter  and  consists  of 
finely  granular  protoplasm  with  a  somewhat  flattened  nucleus.  This  disk 


Germinal  disk  (cytoplasm) 


White  yolk 


Albumen  ("white 


Vitelline  membrane 


White  yolk 


Shell  membrane 
(outer  layer) 


Chalaza 

Shell  membrane 
(inner  layer) 


Yellow  yolk  (deutoplasm) 
FIG.  7. — Diagram  of  a  vertical  section  through  an  unfertilized  hen's  egg.     Bonnet. 

alone  gives  rise  to  the  embryo  proper.  All  the  rest  of  the  mass  consisting  of  a 
vast  number  of  spherules  united  by  a  small  amount  of  cement  substance,  is 
simply  nutritive  material  or  deutoplasm  which  is  later  utilized  for  the  nourish- 
ment of  the  embryo. 

THE  SPERMATOZOON. 

In  marked  contrast  to  the  ovum,  the  spermatozoon  is  one  of  the  smallest  cells 
of  the  body,  being  only  about  fifty  microns  in  length.  The  spermatozoon,  as 
seen  in  the  seminal  fluid,  in  any  of  the  sexual  passages,  or  even  in  the  lumen  of  a 
seminiferous  tubule,  is  a  true  sexual  element,  since  it  has  passed  through  certain 
processes  which  prepare  it  for  union  with  the  mature  ovum.  (See  Spermatogen- 
esis,  Chap.  III.)  Like  the  ovum  the  spermatozoon  is  an  animal  cell  of  which, 
however,  both  cell  body  and  nucleus  have  undergone  important  modifications. 
The  flagellate  spermatozoon,  of  which  the  human  spermatozoon  is  an  example 
(Fig.  8),  resembles  a  tadpole  in  shape  and  like  the  latter  swims  about  by 
means  of  the  undulatory  movements  of  its  long  slender  flagellum  or  tail.  It 
consists  of  (i)  a  head,  (2)  a  middle-piece  or  body  and  (3)  a  tail. 

i.  THE  HEAD.— This  in  the  human  spermatozoon  is  from  three  to  five 
microns  long  and  about  half  as  broad.  On  side  view  it  appears  oval ;  when 


14 


TEXT-BOOK  OF  EMBRYOLOGY. 


Acrosome 


Head 


Anterior  end  knob 
Posterior  end  knob 


seen  on  edge,  it  is  pear-shaped,  the  small  end  being  directed  forward.  It 
consists  mainly  of  nuclear  material  derived  from  the  nucleus  of  the  parent  cell. 
(See  Spermatogenesis.)  A  thin  layer  of  cytoplasm,  the  galea  capitis  or  head- 
cap,  envelops  the  nuclear  material,  while  in 
front  there  is  a  sharp  edge  known  as  the 
apical  body  or  acrosome.  In  contrast  to  the 
nuclear  portion  of  the  head,  which  of  course 
takes  a  basic  stain,  the  acrosome  stains  with 
acid  dyes.  In  some  forms  the  acrosome  is 
much  larger  than  in  man  and  extends 
forward  from  the  head-cap  as  a  long  spear, 
sometimes  barbed — the  perforatorium.  This 
process  perhaps  assists  the  spermatozoon  in 
clinging  to  or  in  burrowing  its  way  into  the 
ovum.  Many  peculiar  types  of  perfora- 
toria,  for  example,  lance-shaped,  awl- 
shaped,  spoon-shaped,  corkscrew-shaped, 
have  been  described  and  have  given  charac- 
teristic names  to  the  spermatozoa  possessing 
them. 

2.  THE  BODY  in  the  human  sperma- 
tozoon is  cylindrical  and  about  the  same 
length  as  the  head.  It  consists  of  a  deli- 
cately fibrillated  cord,  the  axial  thread,  sur- 
rounded by  a  protoplasmic  capsule.  In 
some  forms  (Mammals)  a  short  clear  por- 
tion, the  neck,  unites  the  head  and  body. 
In  the  neck  there  can  sometimes  be  demon- 
strated an  anterior  end  knob  and  one  or 
more  posterior  end  knobs  to  which  is  attached 
the  axial  filament.  In  man  and  in  some 
other  forms,  delicate  fibers — spiral  fibers — 
wdnd  spirally  around  that  portion  of  the 
axial  filament  which  lies  within  the  body. 
At  the  posterior  end  of  the  body,  the  axial 
filament  passes  through  the  end  disk  or  end 
ring. 

3.  THE  TAIL  in  the  human  spermatozoon  is  forty  to  fifty  microns  in  length; 
is  the  direct  continuation  of  the  axial  thread  of  the  body;  and  consists  of  a  main 
segment  thirty-five  to  forty-five  microns  in  length,  and  a  short  terminal 
segment.  As  in  the  body,  the  axial  filament  is  delicately  fibrillated.  Sur- 


Main  segment 
of  tail 


FIG.  8. — Diagram  of  a  human  sperma- 
tozoon.    Me-ves,  Bonnet. 


THE   SEXUAL  ELEMENTS — OVUM  AND   SPERMATOZOON.  15 

rounding  the  axial  filament  is  a  thin  cytoplasmic  membrane  or  capsule 
continuous  with  that  of  the  body.  In  the  human  spermatozoon  it  is  ap- 
parently structureless;  in  other  forms  it  assumes  curious  shapes  as,  for  example, 
the  so-called  membrana  undulatoria,  or  wavy  membrane  of  Amphibia,  or  the  fine 
membrane  of  some  Insects.  The  terminal  segment  consists  of  the  axial  fila- 
ment uncovered  by  any  sheath. 

The  significance  of  the  various  parts  of  the  spermatozoon  can  be  best 
understood  by  reference  to  spermatogenesis  (p.  21). 

Comparing  the  spermatozoon  with  a  cell,  the  head  contains  the  nucleus 
while  the  body  contains  the  centrosome.  It  is  these  parts  of  the  spermatozoon 
which  are  essential  to  fertilization.  The  acrosome  and  the  tail  may  therefore 
be  considered  as  accessory  structures  which  serve  to  bring  and  attach  the 
spermatozoon  to  the  ovum. 

Within  the  tubule  of  the  testis  the  spermatozoa  show  no  evidence  of  motile 
power.  In  the  semen,  however,  which  consists  mainly  of  fluid  secretions  of 
the  accessory  sexual  glands,  they  move  about  freely,  as  also  in  the  fluids  of  the 
female  genital  tract.  Their  speed  has  been  estimated  at  from  1.5  to  3.5  mm. 
per  minute  and  enables  them  to  swim  up  through  the  uterus  and  oviduct,  in 
spite  of  the  fact  that  the  action  of  the  cilia  lining  these  tracts  is  against  them. 

The  life  of  the  spermatozoon  within  the  female  genital  tract  is  not  known. 
Moving  spermatozoa  have  been  found  there  seven  to  eight  days  after  coitus. 
In  one  case  reported  of  removal  of  the  tubes,  living  spermatozoa  were  found 
three  and  one-half  weeks  after  coitus. 

PRACTICAL  SUGGESTIONS. 

The  fresh  unfertilized  eggs  of  the  star-fish  or  sea-urchin  serve  for  general  pictures  of 
alecithal  ova.  They  are  carefully  removed  from  the  animal  and  prepared  in  the  following 
manner.  It  is  best  to  use  slender  vessels  in  order  to  facilitate  changing  the  fluids. 

Formalin  5%  or  Flemming's  fluid,  few  hours. 
Water  (after  Flemming's  fluid  only)  2  or  3  changes,          few  hours. 

Alcohol  70%,  i  or  2  changes,  few  hours. 

Borax  carmin,  24  hours. 
HC1  i%  in  alcohol  70%,                                                  12  to  24  hours. 

Alcohol  70%,  several  changes,  few  hours. 

Alcohol  95%,  few  hours. 

Alcohol  absolute,  few  hours. 

Xylol,  few  hours. 

Thin  balsam,  indefinitely. 

A  small  amount  of  the  balsam  containing  some  of  the  ova  is  taken  up  in  a  pipette,  placed 
on  a  slide  and  covered  with  a  cover-glass. 

For  the  study  of  the  mammalian  (alecithal)  ovum,  the  ovary  of  a  dog  or  cat,  or  of  a  girj 
or  young  woman  may  be  fixed  in  Orth's  fluid,  or  in  Bouin's  fluid  (see  page  631),  embedded 


. 

16  TEXT-BOOK  OF  EMBRYOLOGY. 

and  cut  in  either  celloidin  or  paraffin,  stained  in  haematoxylin  and  eosin  (see  page  636)  and 
mounted  in  xylol-damar. 

The  frog's  eggs  are  good  examples  of  telolecithal  ova  with  a  definite  but  not  complete 
polar  differentiation.  They  may  be  collected  in  ponds  in  the  early  spring  and  preserved 
indefinitely  in  5  per  cent,  formalin.  For  gross  study  a  few  of  the  ova  may  be  separated 
from  the  general  mass  and  examined  under  a  hand  lens.  For  internal  structure,  the  ova 
may  be  carefully  removed  from  the  gelatinous  mass,  stained  in  toto  with  borax  carmin, 
embedded  in  celloidin  or  paraffin,  sectioned,  and  mounted  in  damar.  Ova  fixed  in  any 
osmic  acid  mixture  will  show  the  yolk  granules  stained  black. 

The  various  parts  of  a  hen's  egg  (telolecithal  ovum  with  extreme  polar  differentiation) 
may  be  observed  by  simply  removing  a  part  of  the  shell.  To  study  the  egg,  however,  with- 
out the  secondary  membranes,  it  must  be  seen  in  the  hen's  ovary. 

References  for  Further  Study. 

CONKLIN,  E.  G.:  Organ-forming  Substances  in  the  Eggs  of  Ascidians.  Biol.  Bull., 
Vol.  VIII,  1905. 

KEIBEL,  F.  and  MALL,  F.  P.:  Manual  of  Human  Embryology,  1910.     Vol.  I,  Chap.  I. 

WALDEYER,  W. :  In  Hertwig's  Handbuch  der  vergleichenden  u.  experimentellen  Entwick- 
elungslehre  der  Wirbeltiere.  Bd.  I,  Teil  I,  1903.  Also  contains  extensive  bibliography. 

WILSON,  E.  B.:  The  Cell  in  Development  and  Inheritance.     2d  Ed,,  1900. 


CHAPTER   III. 
MATURATION. 

In  the  preceding  chapter  (p.  10)  it  was  stated  that  in  practically  the  entire 
animal  kingdom,  and  without  exception  in  Vertebrates,  the  condition  essential 
to  the  production  of  a  new  individual  was  the  union  of  two  sexually  different 
cells.  Before  this  can  take  place,  however,  the  sex  cells  must  pass  through 
certain  preliminary  and  preparatory  processes  which  are  known  collectively  as 
reduction  of  chromosomes  or  maturation. 

The  manner  in  which  this  reduction  takes  place  is  in  most  sex  cells  extremely 
difficult  of  demonstration,  this  being  especially  true  in  the  higher  forms,  notably 
in  Mammals.  The  fact,  however,  that  such  reduction  occurs  in  all  cases  in- 
vestigated, where  there  is  sexual  reproduction,  is  undisputed.  The  result  also 
is  invariably  the  same.  The  number  of  chromosomes  in  the  mature  sex  cell  is 
reduced  to  half  the  somatic  number  for  the  species. 

MATURATION  OF  THE  OVUM. 

Because  of  the  difficulties  of  observing  this  process  in  higher  forms,  it  is 
advisable  to  describe  first  the  maturation  of  the  ovum  in  such  a  simple  type  as 
Ascaris.  This  has  become  a  classic  for  the  study  of  maturation  owing  to  the 
fact  that  it  shows  the  various  stages  of  the  process  with  remarkable  clearness. 

In  Ascaris  at  about  the  time  the  spermatozoon  enters  the  ovum,  the  chromatic 
elements  of  the  nucleus  are  found  collected  into  two  groups  and  each  group  in 
turn  composed  of  four  rod-shaped  pieces  (Fig.  g,A,B,C  and  D) .  The  groups  are 
known  as  tetrads,  and  the  number  of  tetrads  is  always  one-half  the  usual  number 
of  chromosomes.  In  this  particular  form  the  usual  number  of  chromosomes  is 
four.  An  achromatic  spindle  next  forms  as  in  ordinary  mitosis,  and  two  of 
the  chromatin  rods  from  each  tetrad  pass  out  into  a  small  mass  of  cytoplasm 
which  becomes  separated  from  the  ovum  (Fig.  9,  E,  F,  G  and  H)  as  the  first 
polar  body.  The  four  chromatin  rods  which  remain  in  the  ovum  constitute  two 
dyads;  each  dyad  representing  one-half  of  a  tetrad.  Closely  following  the 
formation  of  the  first  polar  body  and  without  any  return  of  the  chromatin  to  a 
resting  stage,  the  second  polar  body  is  given  off.  This  is  accomplished  by  two 
chromatin  rods,  one  from  each  dyad,  passing  out  from  the  ovum,  surrounded  by 
a  small  mass  of  cytoplasm, *as  in  the  case  of  the  first  polar  body.  There  thus 
remain  in  the  ovum  two  rods  or  two  chromosomes,  one-half  the  usual  number 

17 


18 


TEXT-BOOK  OF  EMBRYOLOGY. 


(Fig.  9,  /,  /  and  K).  The  somatic  number  of  chromosomes  has  been  reduced 
one-half,  and  the  egg  nucleus — female  pronudeus — is  ready  for  union  with  the 
sperm  nucleus — male  pronucleus. 

Since  the  chromatin  rods  left  after  the  formation  of  the  polar  bodies  are 


FIG.  9. — Maturation  of  the  ovum  of  Ascaris  megalocephala  (bivalens).  Boveri,  Wilson.  A, 
The  ovum  with  the  spermatozoon  just  entering  at  x*  ;  the  egg  nucleus  contains  2  tetrads  (one  not 
clearly  shown),  the  somatic  number  of  chromosomes  being  4.  B,  Tetrads  in  profile.  C,  Tetrads 
on  end.  D,  E,  First  spindle  forming.  F,  Tetrads  dividing.  G,  First  polar  body  formed,  containing 
2  dyads;  2  dyads  left  in  the  ovum.  H,  I,  Dyads  rotating  in  preparation  for  next  division.  J, 
Dyads  dividing.  K,  Each  dyad  divided  into  2  single  chromosomes,  thus  completing  the  reduction. 


MATURATION.  19 

considered  as  chromosomes,  the  question  arises  as  to  the  relation  that  the  rod- 
like  elements  composing  the  tetrads  bear  to  the  chromatin  of  the  nucleus  before 
the  tetrads  are  formed.  In  other  words,  what  is  the  origin  of  the  tetrads  ?  The 
answer  to  this,  even  in  Ascaris,  is  not  quite  clear.  It  is  generally  agreed,  how- 


z.p. 

FIG.  10. — From  section  of  ovum  (primary  oocyte)  of  the  mouse,  showing  first  maturation 
spindle.  Note  the  12  chromatin  segments,  the  somatic  number  of  chromosomes  being  24.  The 
ovum  is  surrounded  by  the  zona  pellucida  (z.p.)  and  the  corona  radiata.  Sobotta. ' 

ever,  that  after  the  formation  of  the  spireme  thread,  the  latter  segments  into 
two  chromatin  rods  instead  of  four;  that  is,  it  segments  into  one-half  the  usual 
number  of  pieces.  Each  piece  splits  longitudinally  and  then  each  resulting 
piece  splits  longitudinally  again.  Thus  each  primary  segment  gives  rise  to 


r* 


FIG.  ii.  —  From  sections  of  ova  of  the  mouse.  The  figure  on  the  left  shows  a  tangential  matu- 
ration spindle  with  12  chromatin  segments.  The  figure  on  the  right  shows  a  tangential  maturation 
spindle  in  which  each  of  the  12  chromatin  segments  has  divided  transversely  into  two  equal  parts, 
thus  forming  24  segments.  Sobotta. 

four  segments  which  constitute  a  tetrad.     From  this  it  is  evident   that  the 
crucial  point  in  reduction  is  the  segmentation  of  the  spireme  thread. 

In  Ascaris,  as  described  above,  reduction  takes  place  by  means  of  tetrad 
formation,  the  tetrads  being  formed  by  a  double  longitudinal  splitting  of  the 


20 


TEXT-BOOK  OF  EMBRYOLOGY. 


primary  chromatin  rods.  Tetrad  formation,  however,  is  of  comparatively  rare 
occurrence,  for  in  most  animals,  especially  in  the  higher  forms,  no  distinct 
tetrads  are  formed.  It  is  possible,  however,  that  certain  chromatin  structures 
in  the  primary  oocyte  may  be  analogous  to  tetrads.  In  the  mouse,  for  example, 
the  most  thoroughly  investigated  mammalian  form,  the  spireme  thread  prob- 


m.pn. 


A 


FIG.  12. — From  sections  of  ova  of  the  mouse,  showing  three  stages  in  the  maturation  process. 

A,  Ovum  showing  prophase  of  maturation  division.    /,  fat;  z.p.,  zona  pellucida. 

B,  Ovum  showing  maturation  spindle  with  chromatin  segments  undivided. 

C,  Ovum  showing  diaster  stage  of  maturation  division,  formation  of  ist  polar  body  (p.b.),  and  sperm 

nucleus  (male  pronucleus,  m.pn.)  just  after  its  entrance.    Sobotta. 

ably  segments  into  one-half  the  usual  number  of  pieces,  but  the  further  behavior 
of  these  pieces  differs  from  their  behavior  in  Ascaris.  Each  chromatin  seg- 
ment is  possibly  equivalent  to  a  tetrad;  and  the  number  of  chromatin  segments 
is  one-half  the  somatic  number  of  chromosomes,  just  as  the  number  of  tetrads 
is  always  one-half  the  somatic  number  of  chromosomes.  When  the  first 


f.pn.  - 


m.pn. 


FIG.  13. — From  sections  of  ova  of  the  mouse,  showing  the  polar  bodies  (p.b.)  and  three  stages  of  the 
male  (m.pn.)  and  female  (f.pn.)  pronuclei.    Sobotta. 

maturation  spindle  forms  in  the  ovum — primary  oocyte — of  the  mouse,  twelve 
chromatin  segments  are  found  grouped  in  the  equatorial  plane  (the  somatic 
number  being  twenty-four)  (Fig.  10).  Each  chromatin  segment  next  divides 
transversely  into  two  equal  parts  (Fig.  n).  One  part  from  each  segment  now 
passes  out  into  a  small  globule  of  cytoplasm  which  becomes  detached  from  the 


MATURATION.  21 

ovum  and  forms  the  first  polar  body  (Fig.  12),  thus  leaving  within  the  ovum 
— secondary  oocyte — twelve  parts  or  pieces.  Closely  following  the  formation 
of  the  first  polar  body,  the  twelve  remaining  pieces  divide  again  transversely 
and  one-half  of  each  piece  passes  out  into  the  second  polar  body  (Fig.  13). 
Within  the  ovum — now  the  mature  ovum — there  still  remain  twelve  pieces  of 
chromatin  or  twelve  chromosomes — one-half  the  somatic  number.  As  a 
matter  of  fact,  Sobotta,  who  studied  the  process  in  the  mouse,  observed  in 
the  majority  of  cases  only  one  polar  body  (Fig.  13,  A).  Later  investigators  have 
suggested  that  the  second  polar  body  also  was  probably  formed  but  at  such  a 
time  or  in  such  a  plane  that  Sobotta  had  failed  to  see  it.  If  only  one  polar 
body  is  formed,  the  reduction  is  atypical ;  but  if,  as  suggested  later,  two  polar 
bodies  are  formed,  it  would  make  the  process  typical.  In  either  case  the  result 
is  the  same  so  far  as  the  number  of  chromosomes  is  concerned,  but  in  the 
former  case  the  bulk  of  chromatin  is  reduced  only  to  one-half,  in  the  latter 
case  it  is  reduced  to  one-fourth  the  original  amount. 

SPERMATOGENESIS. 

The  maturation  of  the  male  sex  cells  in  the  majority  of  forms  is  perhaps 
more  difficult  of  demonstration  than  the  maturation  of  the  female  sex  cells, 
both  on  account  of  the  extreme  minuteness  of  the  former  and  on  account  of  the 
fact  that  it  is  necessary  to  consider  all  the  generations  of  cells  from  the  mature 
spermatozoa  back  to  the  spermatogonia.  In  some  forms  the  reduction  of 
chromosomes  has  been  demonstrated,  and  it  is  reasonable  to  assume  that  it 
occurs  in  all  forms.  In  Ascaris,  for  example,  the  reduction  has  been  clearly 
shown  to  occur,  as  in  the  case  of  the  ovum,  through  tetrad  formation  (Fig.  14). 
In  the  higher  forms,  and  especially  in  Mammals,  the  process  has  not  been 
observed  with  such  accuracy;  but  it  is  possible  in  a  general  way  to  trace  the 
changes  through  which  the  cells  pass  to  arrive  at  the  stage  of  mature  sperma- 
tozoa. 

In  the  mammalian  testis  (Fig.  15,  A)  the  stratified  epithelium  of  the  con- 
voluted seminiferous  tubule  consists  of  two  distinct  kinds  of  cells :  (i)  the 
so-called  supporting  cells  or  cells  of  Sertoli,  and  (2)  the  different  generations  of 
male  sex  cells  or  spermatogenic  cells.  In  a  portion  of  a  tubule  where  active 
formation  of  spermatozoa  is  not  going  on,  the  cells  are  arranged  as  follows. 
Upon  the  basement  membrane  is  a  single  layer  of  small  oval  or  cuboidal 
cells  with  nuclei  rich  in  chromatin.  These  are  known  as  spermatogonia. 
Internal  to  these  are  one  or  two  layers  of  larger  round  or  oval  cells  with  large, 
vesicular,  densely  staining  nuclei,  the  spermatocytes.  Between  these  and  the 
lumen  are  several  layers  of  small,  oval  cells  whose  nuclei  contain  closely-packed 
chromatin  granules.  These  are  the  spermatids.  Usually  the  lumen  of  the 
tubule  contains  a  number  of  mature  spermatozoa,  which  may  lie  either  free  in  the 


22 


TEXT-BOOK  OF  EMBRYOLOGY. 


lumen  or  with  their  heads  embedded  in  the  supporting  cells.  The  supporting 
cells  extend  from  the  basement  membrane  to  the  lumen  of  the  tubule  where 
they  frequently  spread  out  in  a  fan-like  shape. 

The  developmental  cycle  through  which  the  spermatogenic  cells  pass,  in- 
cluding reduction  of  chromosomes,  occurs  in  a  definitely  progressive  manner 


fC* 

e&r**  'iga* 


/  J  K  L 

FIG.  14. — Reduction  of  chromosomes  in  spermatogenesis  in  Ascaris  megalocephala  (bivalens). 
Brauer,  Wilson.  A — G,  Successive  stages  in  the  division  of  the  primary  spermatocyte.  The  original 
reticulum  undergoes  a  very  early  division  of  the  chromatin  granules  which  then  form  a  doubly  split 
spireme  (B).  This  becomes  shorter  (C),  and  then  breaks  in  two  to  form  the  2  tetrads  (D,  in  profile, 
E,  on  end).  F,  G,  H,  First  division  to  form  2  secondary  spermatocytes,  each  receiving  2  dyads.  /, 
Secondary  spermatocyte.  ,  /,  K,  The  same  dividing.  L,  Two  resulting  spermatids,  each  containing 
2  single  chromosomes. 

along  length-segments  of  the  seminiferous  tubule.  Thus  a  particular  cross 
section  may  contain  only  the  earlier  stages  of  spermatogenesis,  the  succeeding 
serial  sections  containing  the  middle  and  later  stages.  After  the  sections  con- 
taining fully  developed  spermatozoa,  the  next  succeeding  sections  contain  the 
early  stages  again. 


MATURATION. 


23 


spz 

spc 


I 

' 


C  D 

FIG.  15. — From   sections  of  seminiferous  tubules  of  Rat,  showing  successive  stages  in  spermato- 

genesis.      Lenhossek. 

A,  Typical  section  showing  clumps  of  spermatozoa  (spz)  with  their  heads  embedded  in  Sertoli  cells; 

several  layers  of  spermatids  (spm);  layer  of  spermatocytes  (spc)  with  nuclei  preparing  for 
division;  layer  of  spermatogonia  (spg)  next  basement  membrane. 

B,  Section  showing  beginning  of  transformation  of  spermatids  (spm)  into  spermatozoa;  spermato- 

cytes (spc)  with  larger  cell  bodies  and  spiremes  in  nuclei. 

C,  Section   showing   large   spermatocytes    (spc)  in   process  of  division;  spermatogonia    (spg)  pre- 

paring for  division  to  form  new  spermatocytes.  Spermatids  of  preceding  stage  (B)  are  repre- 
sented here  by  spermatozoa  (spz). 

D,  Section    showing    further   advance.     The    primary  spermatocytes   of   the  preceding  stage  (C) 

have  divided  to  form  secondary  spermatocytes  and  the  latter  to  form  the  spermatids  (spm) 
represented  here.  During  these  divisions  the  reduction  of  chromosomes  has  taken  place. 
The  spermatogonia  of  the  preceding  stage  have  divided,  one  daughter  cell  from  each  forming  a 
new  spermatocyte  (spc),  the  other  still  remaining  as  a  spermatogonium  (spg). 


24  TEXT-BOOK  OF  EMBRYOLOGY. 

The  spermatogonia  multiply  by  ordinary  mitosis.  During  the  period  of 
sexual  maturity  of  the  individual,  the  spermatogonia  are  constantly  proliferat- 
ing, while  at  the  same  time,  some  of  the  spermatogonia,  ceasing  to  proliferate, 
enter  upon  a  period  of  growth  in  size  (Fig.  17).  When  the  limit  of  this  growth 
is  reached,  these  cells  are  known  as  primary  spermatocytes.  These  large  cells 
have  distinct  nuclear  networks.  As  the  primary  spermatocyte  prepares  for 
division,  the  spireme  thread  probably  segments  into  one-half  the  usual  number 
of  pieces.  As  already  noted,  this  results  in  Ascaris  in  the  formation  of  tetrads. 
The  process  is  not  so  clear,  however,  in  higher  forms,  but  in  all  cases,  whether 
there  is  tetrad  formation  or  not,  the  behavior  of  the  chromatin  is  such  that 
each  daughter  cell — secondary  spermatocyte — receives  one-half  the  usual  num- 
ber of  chromatin  segments.*  Without  any  return  of  the  nucleus  to  the  resting 
state,  each  secondary  spermatocyte  divides  into  two  cells  which  are  known  as 
spermatids,  each  of  which  also  receives  one-half  the  usual  number  of  chromatin 
segments,  or  chromosomes.  Thus  each  primary  spermatocyte  gives  rise  to 
four  spermatids,  each  of  which  contains  one-half  the  somatic  number  of 
chromosomes.  A  careful  study  and  comparison  of  the  stages  represented  in  Fig. 
15,  A,  B,  C  and  D  will  assist  in  understanding  the  processes  of  spermatogenesis. 

After  the  last  spermatocyte  division  and  the  resulting  formation  of  the 
spermatid,  the  nucleus  of  the  latter  acquires  a  membrane  and  intranuclear  net- 
work, thus  passing  into  the  resting  condition.  Without  further  division  the 
spermatid  now  becomes  transformed  into  a  spermatozoon.  This  is  accomplished 
by  rearrangement  and  modification  of  its  component  structures  (Fig.  16). 
The  centrosome  either  divides  completely,  forming  two  centrosomes,  or  partially, 
forming  a  dumb-bell-shaped  body  between  the  nucleus  and  the  surface  of  the 
cell.  The  nucleus  passes  to  one  end  of  the  cell  and  becomes  oval  in  shape. 
Its  chromatin  becomes  very  compact  and  is  finally  lost  in  the  homogeneous 
chromatin  mass  which  forms  the  greater  part  of  the  head  of  the  spermatozoon. 
Both  centrosomes  apparently  take  part  in  the  formation  of  the  middle  piece. 
The  one  lying  nearer  the  center  becomes  disk-shaped  and  attaches  itself  to  the 
posterior  surface  of  the  head.  The  more  peripheral  centrosome  also  becomes 
disk-shaped  and  from  the  side  directed  away  from  the  head  a  long  delicate 
thread  grows  out — the  axial  filament.  The  central  portion  of  the  outer  cen- 
trosome next  becomes  detached  and  in  Mammals  forms  a  knob-like  thickening — 
end  knob — at  the  central  end  of  the  axial  filament.  In  Amphibians  this  part  of 
the  outer  centrosome  appears  to  pass  forward  and  to  attach  itself  to  the  inner 
centrosome.  In  both  cases  the  rest  of  the  outer  centrosome  in  the  shape  of  a 
ring  passes  to  the  posterior  limit  of  the  cytoplasm.  As  the  two  parts  of  the 
posterior  centrosome  separate,  the  cytoplasm  between  them  becomes  reduced 
in  amount,  at  the  same  time  giving  rise  to  a  delicate  spiral  thread — the  spiral 

*According  to  Bonnet,  the  reduced  number  of  chromosomes  first  appears  in  the  spermatids. 


MATURATION. 


25 


filament — which  winds  around  the  axial  filament  of  the  middle  piece.  Mean- 
while the  axial  filament  has  been  growing  in  length  and  part  of  it  projects  be- 
yond the  limits  of  the  cell.  The  cytoplasm  remaining  attached  to  the  anterior 
part  of  the  filament  surrounds  it  as  the  sheath  of  the  middle  piece.  In  Mam- 
mals there  appears  to  be  more  cytoplasm  than  is  needed  for  the  formation  of  the 
sheath  of  the  middle  piece,  and  a  large  part  of  it  degenerates  and  is  cast  aside. 


Head 

Anterior  end  knob 
Posterior  end  knob 

Body 
End  ring 


Tail 


Head 

.  Anterior  end  knob 
Posterior  end  knob 
5"  End  ring 


Tail 


Nucleus 


t~  Cytoplasm 

L-  Proximal  centrosome 


Distal  centrosome 


FIG.    16. — Transformation  of    a  spermatid  into  a  spermatozoon   (human).     Schematic. 

Meves,  Bonnet. 

The  sheath  which  surrounds  the  main  part  of  the  axial  filament  appears  in  some 
cases  at  any  rate  to  develop  from  the  filament  itself.  The  galea  capitis  or 
delicate  film  of  cytoplasm  which  covers  the  head  is  undoubtedly  a  remnant  of 
the  cytoplasm  of  the  spermatid. 

The  developing  spermatozoa  lie  with  their  heads  directed  toward  the  base- 
ment membrane,  and  attached,  probably  for  purposes  of  nutrition,  to  the  free 
ends  of  the  Sertoli  cells  (Fig.  15).  Their  tails  often  extend  out  into  the  lumen 
of  the  tubule.  When  fully  developed  they  become  detached  from  the  Sertoli 
cells  and  lie  free  in  the  lumen  of  the  tubule. 


26 


TEXT-BOOK  OF  EMBRYOLOGY. 


Comparing  maturation  in  the  male  and  female  sex  cells,  it  is  to  be  noted 
that  the  descendants  of  the  primordial  germ  cells,  the  spermatogonia  and  the 
ob'gonia,  proliferate  by  ordinary  mitotic  division,  with  the  preservation  of  the 
somatic  number  of  chromosomes,  up  to  a  certain  definite  period  in  their  life 
history.  They  then  cease  proliferating  for  a  time  and  enter  upon  a  period  of 
growth  in  size  (Fig.  17).  The  results  of  this  growth  are  the  primary  spermato- 
cyte  and  the  ovarian  egg  or  primary  oocyte.  When,  however,  the  primary 
spermatocyte  and  the  primary  oocyte  prepare  for  division,  the  nuclear  reticulum 
in  each  case  resolves  itself  into  one-half  the  somatic  number  of  chromosomes, 


A 

•    A    , 

Spermatogonia 

'\  /\ 

•  Prolifera- 
tion 

Oogonia 

"A    \ 

Proliferation 

A 

A  /\  l\ 

-—  •         •         •        • 

/I  A  /\  l\ 

Primary 
spermatocyte 

(1      ' 

>  Growth 

.  £ 

Primary   ^ 
oocyte 

i 

Growth 

-A    ! 

A 

spermatocyte 

A     l\ 

/  \     /  \ 

•         k         A        A 

Secondary 

-i*\ 

1      1      1 

oocyte 

W     A 

a  ura  ion 

1      1      1      I 

-  -  »        4        4        » 

formation 

Mature 
ovum 

A  •  /\ 

Spermatozoon 

(Hi 

FIG.  17. — Diagrams  representing  the  histogenesis  of  (a)  the  female  sex  cells  and  (b)  the  male  sex 

cells.     Modified  from  Boveri. 


and  this  reduced  number  is  given  to  each  of  the  resulting  secondary  spermato- 
cytes  and  secondary  oocytes. 

There  is,  however,  this  marked  peculiarity  in  the  division  of  the  primary 
oocyte,  in  addition  to  the  reduction  in  chromosomes,  that  while  the  di- 
vision of  the  nuclear  material  (chromosomes)  is  equal,  the  division  of  the 
cytoplasm  is  very  unequal,  most  of  the  latter  remaining  in  one  cell,  usually 
designated  the  secondary  oocyte  proper.  The  other  cell  is  of  course  small, 
owing  to  its  lack  of  cytoplasm,  and  is  extruded  from  the  oocyte  proper  as  the 
first  polar  body  (Figs.  9,  12,  13  and  17).  In  the  next  division,  that  of  the  second- 
ary oocyte,  a  similar  condition  obtains.  Each  resulting  cell  contains  the  re- 
duced number  of  chromosomes,  but  one  of  the  cells  is  large  containing  nearly 
all  the  cytoplasm  and  is  the  mature  egg  cell,  while  the  other  is  small  owing  to  its 
small  amount  of  cytoplasm,  and  is  extruded  from  the  larger  cell  as  the  second 


MATURATION.  27 

polar  body  (Figs.  9,  12,  13  and  17).  In  some  cases  the  first  polar  body  divides, 
giving  to  each  resulting  cell  the  reduced  number  of  chromosomes.  There  have 
thus  resulted  from  the  reduction  division  in  the  ob'cyte,  three  or  four  cells 
(Fig.  17).  One  of  these  is  the  mature  ovum  containing  one-half  the  somatic 
number  of  chromosomes,  the  other  two  or  three  are  the  cast  off  and  apparently 
useless  polar  bodies,  each  of  which  contains  one-half  the  somatic  number  of 
chromosomes.  The  primary  spermatocyte,  on  the  other  hand,  gives  rise  to 
four  cells  which  are  equal  in  size  as  well  as  in  their  chromatin  content  (Fig.  17). 

There  thus  develop  from  both  spermatocyte  and  oocyte  four  structures, 
each  containing  one-half  the  somatic  number  of  chromosomes,  only,  as  already 
noted,  in  the  case  of  the  spermatocyte,  all  four  of  the  resulting  products  of 
division  become  functional  as  spermatozoa,  while  in  the  case  of  the  oocyte  only 
one  product,  the  mature  egg  cell,  becomes  of  functional  value.  '(Compare 
Fig.  17  a  and  b.) 

The  time  of  formation  of  the  polar  bodies  differs  for  different  eggs.  In 
some  cases  both  polar  bodies  are  extruded  before  the  entrance  of  the  spermato- 
zoon. In  other  cases  one  polar  body  is  formed  before,  the  other  after  the 
entrance  of  the  spermatozoon.  In  still  other  eggs  both  polar  bodies  are  formed 
after  the  entrance  of  the  spermatozoon. 

From  the  above  description  it  is  evident  that  the  phenomena  of  maturation 
are  essentially  similar,  and  the  process  itself  is  identical  in  both  male  and  female 
sex  cells.  The  details  of  the  process  vary,  but  the  result — the  reduction  of  the 
number  of  chromosomes  in  the  mature  sex  cell  to  one-half  the  number  char- 
acteristic for  other  cells  of  the  species — is  always  the  same. 

The  exact  manner  in  which  reduction  takes  place  has  been  the  subject  of 
much  investigation  and  controversy  and  has  as  yet  been  determined  for  com- 
paratively few  forms.  In  the  higher  animals  the  point  at  which  the  actual 
reduction  in  number  of  chromosomes  takes  place  is  usually  two  generations 
of  cells  before  the  formation  of  the  mature  sex  cells.  The  behavior  of  the 
chromatic  spireme  of  the  oocyte  or  of  the  spermatocyte,  as  it  breaks  up  into  one- 
half  the  somatic  number  of  chromosomes,  varies  sufficiently  to  allow  two 
general  types  of  maturation  to  be  distinguished,  known,  respectively,  as  reduc- 
tion with  tetrad  formation  and  reduction  without  tetrad  formation. 

In  reduction  with  tetrad  formation  the  spireme  (primary  oocyte  or  primary 
spermatocyte)  segments  into  the  reduced  number  of  chromatin  masses,  each  one 
of  which  divides  into  four  pieces  and  is  consequently  known  as  a  tetrad.  The 
two  maturation  divisions  now  follow,  the  second  following  the  first  rapidly  with- 
out reconstruction  of  a  nuclear  reticulum.  In  the  first  of  these  each  tetrad 
divides  equally,  giving  rise  to  two  dyads,  each  consisting  of  two  pieces  of 
chromatin  and  each  passing  to  one  of  the  daughter  cells  (secondary  oocyte, 
first  polar  body,  spermatocyte)  (Figs.  9  and  14).  In  the  second  maturation 


28  TEXT-BOOK  OF  EMBRYOLOGY. 

division  each  dyad  gives  one  of  its  pieces  to  each  daughter  cell  (mature  ovum, 
second  polar  body,  spermatid)  (Figs.  9  and  14). 

In  reduction  without  tetrad  formation,  the  spireme  segments  into  the  re- 
duced number  of  pieces.  Each  of  these  segments,  however,  does  not  show  an 
immediate  differentiation  into  four  pieces  to  form  a  tetrad,  as  in  the  case  of 
reduction  with  tetrad  formation;  but  in  the  first  maturation  division  each 
chromatin  segment  divides  equally,  giving  half  its  substance  to  each  daughter 
cell.  Then  there  may  be  a  more  or  less  complete  reconstruction  of  the  nucleus. 
Finally,  in  the  second  maturation  division,  each  of  the  halves  of  the  original 
chromatin  segments  divides  again,  one  part  passing  to  each  daughter  cell. 

Comparison  of  the  two  types  of  reduction  makes  evident  the  fact  that  there 
is  no  essential  difference  between  them,  other  than  the  time  of  division  of  the 
reduced  number  of  chromatin  masses  into  their  ultimate  number  for  distribu- 
tion to  the  four  granddaughter  cells.  In  reduction  with  tetrad  formation,  the 
four  ultimate  divisions  are  evident  from  the  first.  In  reduction  without  tetrad 
formation  no  such  subdivision  is  apparent,  the  division  of  each  chromatin  mass 
into  two  being  accomplished  apparently  by  the  first  maturation  division  and 
into  the  final  four  of  the  mature  cell's,  by  the  second  maturation  division. 

The  apparent  difference  between  male  and  female  maturation — the  single 
functional  cell  in  the  female  as  contrasted  with  the  four  in  the  male — loses  some 
of  its  significance  when  one  notes  that  in  some  forms  the  polar  bodies  are  not 
so  rudimentary  as  is  generally  the  case.  Thus  in  certain  forms  one  or  more  of 
the  polar  bodies  may  develop  into  cells  very  similar  to  the  mature  egg  cell,  may 
be  penetrated  by  spermatozoa,  and  may  even  become  fertilized  and  proceed  a 
short  distance  in  segmentation.  There  is  thus  warrant  for  considering  the 
polar  bodies  rudimentary  or  abortive  ova. 

Of  interest  in  connection  with  the  apparent  necessity,  in  sexual  reproduction, 
that  the  egg  rid  itself  of  the  polar  bodies  before  the  female  pronucleus  is  ready 
for  union  with  the  male  pronucleus,  is  the  fact  that  in  certain  parthenogenetic 
eggs  only  a  single  polar  body  is  extruded,  while  the  eggs  of  the  same  species 
which  are  to  be  fertilized  produce  two  polar  bodies;  also  that  in  certain  cases  of 
parthenogenesis  the  second  polar  body  has  been  shown  to  form  what  is  ap- 
parently a  pronucleus,  so  that  there  are  two  pronuclei  within  the  egg  cytoplasm, 
both  derived  from  the  secondary  oocyte.  These  unite  to  form  the  segmenta- 
tion nucleus,  the  second  polar  body  thus  acting  the  part  of  the  male  pronucleus. 

A  brief  discussion  of  accessory  chromosomes  will  be  found  under  the 
head  "Determination  of  Sex"  in  the  chapter  (XV)  on  the  Urogenital  System. 

Theoretical  Aspects  of  Reduction. 

When  we  come  to  consider  why  reduction  of  chromosomes  occurs,  we  are  led  into  a. 
maze  of  conflicting  hypotheses.  The  field  is  purely  speculative  in  character.  Some  of 


MATURATION.  99 

the  hypotheses  have  received  support  from  observation,  others  are  still  hypotheses  in  the 
strictest  sense  of  the  word. 

Some  of  the  earlier  investigators  interpreted  reduction  merely  as  a  means  to  prevent  the 
summation  of  the  nuclear  mass  in  succeeding  generations,  or  in  other  words,  as  a  means  to 
prevent  the  doubling  of  the  number  of  chromosomes  in  each  succeeding  generation.  For 
if  there  were  no  reduction,  the  egg  cell  and  the  sperm  cell  each  would  bring  to  the  segmenta- 
tion nucleus  the  full  amount  of  chromatin  or  the  somatic  number  of  chromosomes.  This 
would  result  in  the  doubling  of  the  chromatin  mass  at  each  fertilization.  While  reduction 
does,  as  a  matter  of  fact,  prevent  this  summation,  the  inadequacy  of  this  explanation  is 
apparent  when  one  considers  that  in  the  vast  majority  of  cases  the  mass  reduction  is  not 
one-half  but  three-fourths,  and  furthermore  that  mass  reduction  really  means  but  little 
because  the  bulk  of  the  nuclear  substance  may  increase  or  decrease  enormously  at  different 
periods  in  the  life  history  of  the  cell. 

Another  interesting  view  first  held  by  Minot,  and  later  adopted  by  others,  was  that  the 
ordinary  cell  is  bisexual  or  hermaphroditic,  and  that  maturation  is  an  effort  on  the  part 
of  the  germ  cells  to  rid  themselves  of  the  opposite  sexual  elements,  i.e.,  the  ovum  rids  itself 
of  its  male  elements  to  become  a  true  female  sex  cell;  the  spermatozoon  of  its  female 
elements,  to  become  a  true  male  sex  cell.  This  theory  also  met  with  a  serious  objection 
when  it  was  found  that  four  functional  spermatozoa  are  derived  from  a  single  primary 
spermatocyte.  The  fact  that  female  qualities  are  transmitted  by  the  male  germ  cell  and  male 
qualities  by  the  female  germ  cell  is  also  opposed  to  this  theory. 

The  most  modern  theory  is  extremely  complex  and  is  closely  associated  with,  even  forms 
a  part  of,  the  modern  ideas  of  inheritance.  Weismann  first,  in  1885,  considered  the  deeper 
meaning  of  reduction  and  set  forth  his  views  in  an  article  of  highly  speculative  character, 
but  which  gave  great  stimulus  to  further  study  of  the  problem.  Weismann's  first  assump- 
tion was  that  "Chromatin  is  not  a  uniform  and  homogeneous  substance,  but  differs  quali- 
tatively in  different  regions  of  the  nucleus;  that  the  collection  of  the  chromatin  into  the 
spireme  thread  and  its  accurate  division  into  halves  is  meaningless  unless  the  chromatin  in 
different  regions  of  the  thread  represents  different  qualities  which  are  to  be  divided  and 
distributed  to  the  daughter  cells  according  to  some  definite  law."  He  argued  that  if  the 
chromatin  were  the  same  throughout,  mitosis  would  be  superfluous  and  direct  cell  division 
would  be  sufficient.  The  real  starting-point  of  Weismann's  theory  is  that  the  chromatin  is  a 
colony  of  minute  particles — biophores — each  of  which  has  the  power  of  developing  some 
quality.  The  biophores  are  grouped  together  into  larger  masses  or  determinants,  and  the 
latter  are  grouped  to  form  ids.  The  ids  are  identified  with  the  visible  chromatin  granules. 
Each  id  is  assumed  to  possess  potentially  the  complete  architecture  of  the  species,  i.e.,  each 
id  has  the  power  of  determining  the  development  of  all  the  qualities  characteristic  of  the 
species.  The  ids  differ  slightly  from  one  another  according  to  individual  variations  within 
the  species,  and  are  arranged  in  a  linear  manner  to  form  the  chromosomes.  Thus  each 
chromosome  is  a  group  of  slightly  different  germ-plasms  and  differs  qualitatively  from  all 
others. 

The  interpretation  of  these  hypotheses  and  their  formulation  into  a  theory  leads  to  still 
greater  complexity.  If  there  were  no  reduction  and  each  germ  nucleus  brought  to  the 
segmentation  nucleus  the  full  amount  of  chromatin,  the  number  of  chromosomes  would  be 
doubled  and  consequently  the  number  of  ids.  And  since  each  id  has  the  power  of  deter- 
mining the  development  of  all  the  qualities  of  the  species,  an  infinite  complexity  would  arise 
after  a  few  generations.  By  reducing  the  ids  both  in  size  and  in  number  in  each  germ  cell, 
the  tendency  toward  this  infinite  complexity  would  be  held  in  check.  Thus  on  the  assump- 


30 


TEXT-BOOK  OF  EMBRYOLOGY. 


tion  that  the  ids  are  arranged  in  linear  series  in  the  chromosomes,  Weismann  ventured  the 
prediction  that  two  forms  of  mitosis  would  be  found  to  occur.  One  would  be  a  longitudinal 
splitting  so  that  each  daughter  nucleus  would  receive  one-half  the  amount  of  each  id.  This 
form  of  division  was  known  at  that  time  and  is  characteristic  of  ordinary  mitosis.  The 
other  form  would,  he  suggested,  be  such  as  to  give  each  daughter  nucleus  one-half  the  number 
of  ids.  This  might  be  brought  about  either  by  transverse  division  of  the  chromosomes 
or  by  the  elimination  of  one-half  the  number  of  chromosomes.  This  form  of  division  was 
not  known  at  that  time  and  the  fulfillment  of  this  second  part  of  Weismann's  predictions 
has  been  one  of  the  most  remarkable  discoveries  in  cytology,  for  it  has  been  demonstrated 
for  some  forms  at  least  that  transverse  division  of  chromosomes  does  actually  occur. 

Weismann's  views  form  a  wonderfully  ingenious  theory  against  which  there  is  thus  far 
no  structural  ground  for  opposition.  Indeed,  some  known  facts  are  in  its  favor.  Whether, 
however,  these  facts  possess  the  significance  which  Weismann  attributed  to  them  is  still  an 
open  question. 


Germinal 

epithelium 


FIG.   18. — From    section   of    human    ovary,  showing    mature    Graafian  follicle    ready  to  rupture. 

Kollmann's  Atlas. 


OVULATION  AND  MENSTRUATION. 

By  ovulation  is  meant  the  periodic  discharge  of  the  ovum  from  the  Graafian 
follicle  and  ovary.  By  menstruation  is  meant  the  periodic  discharge  of  blood 
from  the  uterus  associated  with  structural  changes  in  the  uterine  mucosa.  The 
two  phenomena  are  usually  associated  although  either  may  occur  independ- 
ently of  the  other.  They  normally  occur  every  twenty-eight  days.  That 
ovulation  and  menstruation  are  not  necessarily  dependent  upon  each  other 
and  that  either  may  occur  without  the  other  has  been  proved  by  a  number  of 


MATURATION. 


31 


observations;  thus  the  occurrence  of  fertilization  during  lactation  when  the 
menstrual  function  is  in  abeyance;  the  occurrence  of  impregnation  in  young 
girls  before  the  onset  of  the  menstrual  periods  and  in  women  a  number  of  years 
after  the  menopause.  Leopold  reports  the  examination  of  twenty-nine  pairs  of 
ovaries  on  successive  days  after  menstruation  and  the  finding  of  Graafian 
follicles  just  ruptured  or  just  ready  to  rupture  on  the  eighth,  twelfth,  fifteenth, 
eighteenth,  twentieth  and  thirty-fifth  days.  He  reports  also  five  cases  in  which 
there  were  no  evidences  of  ovulation  during  menstruation. 

At  the  time  of  ovulation  the  mature  follicle,  which  has  a  diameter  of  8  to  12 
mm.,  occupies  the  entire  thickness  of  the  ovarian  cortex,  its  theca  being  in  con- 


FIG.  19. — Showing  ovary  opened  by  longitudinal  incision.  The  ovum  has  escaped  through  the 
tear  in  the  surface  of  the  ovary.  The  cavity  of  the  follicle  is  filled  with  a  clot  of  blood  (corpus  haemor- 
rhagicum)  and  irregular  projections  composed  of  lutein  cells.  Kollmann's  Atlas. 

tact  with  the  tunica  albuginea  (Fig.  18).  Thinning  of  the  follicular  wall  nearest 
the  surface  of  the  ovary,  and  increase  in  the  amount  of  the  liquor  folliculi,  thus 
causing  increased  intrafollicular  pressure,  finally  result  in  rupture  of  the 
follicle  through  the  surface  of  the  ovary  and  the  escape  of  the  ovum  together 
with  the  liquor  folliculi  and  some  of  the  follicular  ceils. 

The  escaped  ovum  normally  passes  into  the  fimbriated  end  of  the  Fallopian 
tube  and  so  to  the  uterus.  In  exceptional  cases  it  may  remain  in  the  tube  after 
fertilization  and  so  give  rise  to  a  tubal  pregnancy,  or,  falling  into  the  abdomi- 
nal cavity  and  becoming  there  fertilized,  to  an  abdominal  pregnancy.  Both  are 
known  as  ectopic  gestations. 

As  the  ovum  escapes  from  the  follicle  there  is  more  or  less  bleeding  into  the 
follicle  from  the  torn  vessels  of  the  theca.  Closure  of  the  opening  in  the 
follicle  results  in  a  closed  cavity  containing  a  blood  clot,  the  corpus  (Fig.  19) 


32 


TEXT-BOOK  OF  EMBRYOLOGY. 


h&morrhagicum,  which  then  becomes  gradually  transformed  into  the  corpus 
luteum. 

The  transformation  of  the  corpus  haemorrhagicum  into  the  corpus  luteum 
(Figs.  20  and  21)  is  brought  about  by  ingrowths  of  strands  of  connective  tissue 
from  the  inner  layer  of  the  theca  and  the  replacement  of  the  remainder  of  the 
clot  by  large  yellowish  cells  containing  pigment  (lutein  granules)  and  known  as 
lutein  cells.  The  lutein  cells  are  considered  by  some  as  derived  from  the  con- 
nective tissue  cells  of  the  theca,  by  others  as  due  to  proliferation  of  the  cells  of 
the  stratum  granulosum.  Degeneration  and  absorption  of  the  tissues  of  the 


Point  of  rupture 


Lutein  cells 


Corpus  haemorrhagicum 


Blood  vessel  of  theca  « 


Cavity  of  follicle 


Theca  folliculi 


Ovarian  stroma 


Stratum  granulosum 


FIG.  20. — From  section  of   human  ovary,   showing  early  stage   in  formation  of  corpus  luteum. 

Kollmann's  Atlas. 

corpus  luteum  follows,  resulting  in  shrinkage,  and  loss  of  its  characteristic 
yellow  color.  The  whitish  body  resulting  is  known  as  the  corpus  albicans  and 
is  itself  in  turn  either  wholly  absorbed  or  represented  only  by  a  small  scar  of 
fibrous  tissue. 

The  rapidity  with  which  the  changes,  both  constructive  and  destructive, 
take  place  in  the  corpus  luteum,  appears  to  be  largely  dependent  upon  whether 
the  egg  which  escaped  from  the  follicle  is  or  is  not  fertilized.  If  ovulation  is  not 
followed  by  fertilization  the  corpus  luteum  reaches  the  height  of  its  development 
in  about  twelve  days,  and  within  a  few  weeks  has  almost  wholly  disappeared. 
If,  on  the  other  hand,  pregnancy  supervenes,  the  corpus  luteum'  becomes  much 
larger,  does  not  reach  its  maximum  development  until  the  fifth  or  sixth  month 
and  is  still  present  at  the  end  of  pregnancy.  The  above  differences  have  led  to 
the  distinction  of  the  corpus  luteum  of  pregnancy  or  the  true  corpus  luteum,  and 


MATURATION. 


33 


the  corpus  luteum  of  menstruation,  or  the  false  corpus  luteum,  although  there 
are  no  actual  microscopic  differences  between  the  two. 


Point  of  rupture 


, 
Connective  tissue  - — ±  X""1"*', 

oiff9* 


Connective  tissue 
from  theca 


Theca  folliculi 


Remnant  of  corpus 
haemorrhagicum 


Blood  vessels 
of  theca 


FIG.  21. — From  section  of   human  ovary,  showing   later  stage  of  corpus  luteum  than  Fig.  20. 

Kollmann's  Atlas. 

PRACTICAL  SUGGESTIONS. 

The  reduction  of  chromosomes  is  beautifully  illustrated  in  Ascaris  megalocephala 
(bivalens).  This  species  of  Nematode  is  parasitic  in  the  intestine  of  the  horse  and  can 
usually  be  procured  by  a  veterinarian.  The  oviducts  are  carefully  removed  and  treated 
as  follows: 

Gilson's  alcohol -acetic-sublimate  mixture,  15  to  30  minutes. 

70%  alcohol,  with  little  tincture  iodine,  several  changes,  24  hours. 

70%  alcohol,  indefinitely. 

Borax-carmin,  24  hours. 

i%  HC1  in  70%  alcohol,  24  hours. 

Absolute  alcohol  and  glycerin,  equal  parts,  24  hours. 

Glycerin,  indefinitely. 

Mounting  for  study  is  carried  out  as  follows:     Cut  the  oviduct  into  about  six  pieces  of 

equal  length,  being  careful  to  keep  the  pieces  in  order.     Cut  a  small  bit  from  one  of  the 

pieces,  gently  shake  some  of  the  ova  into  a  small  drop  of  glycerin  on  a  slide  and  carefully 

apply  a  glass.     Pressure  on  the  cover-glass  will  crush  the  ova.     Ova  from  all  the  pieces  are 


34  TEXT-BOOK  OF  EMBRYOLOGY. 

treated  in  the  same  manner.  For  permanent  mounts  the  cover-glasses  should  be  cemented. 
The  first  (most  cranial)  piece  will  show  the  sperm  in  the  ovum  and  the  nucleus  of  the 
latter  in  the  resting  or  spireme  stage.  The  second  piece  will  show  a  distinct  membrane 
around  the  ovum,  the  sperm  head,  and  the  chromatin  of  the  egg  nucleus  arranged  in 
tetrads.  The  third  piece  will  show  the  membrane,  the  sperm  nucleus  as  a  fainter  structure, 
and  the  first  maturation  spindle.  The  fourth  piece  will  show  the  membrane,  the  sperm 
nucleus  still  fainter,  the  first  polar  body,  and  also  the  second  maturation  spindle.  The 
fifth  piece  will  show  the  membrane,  the  very  faint  sperm  nucleus,  the  first  polar  body  some- 
where around  the  periphery  of  the  ovum,  the  second  polar  body,  and  often  two  chromosomes 
remaining  in  the  ovum.  The  sixth  piece  (near  the  junction  of  the  two  oviducts)  will  often 
show  both  polar  bodies  and  the  two  pronuclei  (with  no  apparent  difference  between  them) 
in  the  resting  stage.  It  should  be  borne  in  mind  that  the  maturation  process  goes  on  pro- 
gressively from  the  cranial  to  the  caudal  ends  of  the  oviducts,  so  that  it  is  possible  to  find 
other  stages  between  those  mentioned. 

Maturation  in  a  mammalian  ovum  is  probably  best  seen  in  the  mouse.  The  ovaries 
of  a  mouse  are  fixed  in  Flemming's  fluid,  cut  in  either  celloidin  or  paraffin  and  stained 
with  Heidenhain's  haematoxylin  (see  Appendix).  In  some  of  the  sections  ova  are  likely  to 
be  found  which  will  show  maturation  spindles,  or  polar  bodies,  or  some  intermediate  stages. 

Owing  to  their  extreme  minuteness,  the  study  of  the  maturation  processes  in  the  sperm 
cells  is  much  more  difficult  than  in  the  ova  and,  furthermore,  since  each  primary  spermato- 
cyte  gives  rise  to  four  spermatids  and  each  spermatid  is  transformed  directly  into  a  sperma- 
tozoon, it  is  necessary  to  consider  all  the  generations  of  cells  from  the  spermatozoa  back 
to  the  spermatogonia. 

Instructive  specimens  may  be  obtained  by  fixing  small  pieces  of  a  fresh  human  testis  in 
Orth's  fluid,  cutting  thin  sections  in  celloidin  and  staining  with  haematoxylin-eosin  (see 
Appendix). 

Better  results  may  be  obtained  from  the  testis  of  some  small  animal.  Remove  imme- 
diately the  testis  of  a  recently  killed  mouse  or  rat,  make  an  incision  to  insure  quick  penetration 
of  the  fixative  and  fix  in  Flemming's  fluid.  Cut  thin  sections  in  paraffin  and  stain  with 
Heidenhain's  haematoxylin  (see  Appendix).  Different  seminiferous  tubules  will  show  dif- 
ferent stages  in  the  development  of  the  spermatozoa.  It  is  scarcely  possible  in  these  prepa- 
rations to  trace  the  actual  process  of  reduction  of  chromosomes. 

References  for  Further  Study. 

BOVERI,  T.:  Zellstudien.     Jena,  1887-1901. 

CHILD,  C.  M.:  Studies  on  the  Relation  between  Amitosis  and  Mitosis.  Biolog.  Bull., 
Vol.  XII,  Nos.  2,  3,  4;  Vol.  XIII,  No.  3,  1907. 

CONKLIN,  E.  G.:   The  Embryology  of  Crepidula.     Jour,  of  Morphol.,  Vol.  XIII,  1897. 

HERTWIG,  R.:  Eireife,  Befruchtung  u.  Furchungsprozess.  In  Hertwig's  Handbuch  der 
•vergleichenden  u.  experimentellen  Entwickelungslehre  der  Wirbeltiere.  Bd.  I,  Teil  I,  1903. 
Also  contains  extensive  bibliography. 

SOBOTTA,  J. :  Die  Befruchtung  und  Furchung  des  Eies  der  Maus.  Archiv  ).  mik.  Anatomic, 
Bd.  XLV,  1895. 

SOBOTTA,  J.:  Ueber  die  Bildung  des  Corpus  luteum  beim  Meerschweinchen.  Anal. 
Hejte,  Bd.  XXXII,  Heft  XCVI,  1906. 

VON  LENHOSSEK,  M.:  Untersuchungen  iiber  Spermatogenese.  Archiv.  }.  mik.  Anatomic, 
Bd.  LI,  1898. 

WILLIAMS,  J.  W.:  Text -book  of  Obstetrics.     New  York,  1903. 

WILSON,  E.  B.:  The  Cell  in  Development  and  Inheritance.     2d  Ed.,  1900. 


CHAPTER  IV. 
FERTILIZATION. 

Mitosis,  as  described  in  Chapter  I,  is  the  process  by  which  cells  proliferate 
to  form  the  various  tissues  and  organs  and  to  take  the  place  of  cells  worn  out 
in  the  carrying  on  of  their  labors  or  destroyed  by  injury.  It  is  constantly  going 
on  throughout  the  life  of  the  individual.  Attention  has  been  called  to  the  fact 
that  in  all  such  reproduction  there  is  a  constantly  maintained  somatic  number  of 
chromosomes.  This  has  been  seen  to  hold  true  up  to  the  formation  of  the 
mature  germ  cells — the  mature  ovum  and  the  spermatozoon,  each  of  which 
contains  one-half  the  somatic  chromosome  number.  In  all  sexual  reproduction 
the  starting  point  of  the  new  individual,  that  is,  the  formation  of  the  single  cell 
from  which  all  the  tissues  and  organs  develop,  is  the  union  of  two  mature  germ 
cells,  the  spermatozoon  and  the  ovum,  one  from  the  male  the  other  from  the 
female.  This  union  is  known  as  fertilization  and  the  resulting  cell  is  the 
fertilized  ovum. 

The  details  of  the  process  vary  in  different  animals.  Its  essence  is  the 
entrance  of  the  spermatozoon  into  the  ovum  and  the  union  of  the  nucleus  of  the 
spermatozoon  with  the  nucleus  of  the  ovum.  At  the  time  of  its  entrance  into 
the  egg,  the  sperm  head  is  small  and  its  chromatin  extremely  condensed 
(Fig.  22,  2).  Soon  after  entering  the  ovum,  however,  the  sperm  head  un- 
dergoes development  into  a  typical  nucleus,  the  male  pronucleus  (Figs.  22,  3, 
and  13,  C).  This  male  pronucleus  is  to  all  appearances  exactly  similar  in 
structure  to  the  nucleus  of  the  egg,  which  latter  is  now  known  as  the  female 
pronucleus.  The  chromatin  networks  in  both  pronuclei  next  pass  into  the 
spireme  stage,  the  spiremes  segmenting  into  chromosomes  of  which  each  pro- 
nucleus  contains  one-half  the  somatic  number.  The  nuclear  membranes  mean- 
while disappear  and  the  chromosomes  lie  free  in  the  cytoplasm.  During  these 
changes  in  the  pronuclei,  the  amphiaster  has  formed  and  the  male  and  the 
female  chromosomes  mingle  in  its  equatorial  plane  (Fig.  22,  5).  At  this  stage 
no  actual  differentiation  can  be  made  between  male  chromosomes  and  female 
chromosomes,  the  differentiation  shown  in  Fig.  22,  5,  being  schematic. 
The  picture  is  now  that  of  the  end  of  the  prophase  of  ordinary  mitosis, 
the  somatic  number  of  chromosomes  being  arranged  in  a  plane  midway 
between  the  two  centrosomes.  With  the  mingling  of  male  and  female  chro- 
mosomes fertilization  proper  comes  to  an  end.  The  further  steps  are  also 
identical  with  those  of  ordinary  mitosis.  Each  chromosome  splits  longitudinally 

35 


36 


TEXT-BOOK  OF  EMBRYOLOGY. 


into  two  exactly  similar  parts  (Fig.  22,  5),  one  of  which  is  contributed  to 
each  daughter  nucleus  (Fig.  22,  6),  and  the  cell  body  divides  into  two  equal 
parts.  (For  details  of  succeeding  anaphase  and  telophase  see  p.  6.)  There 
thus  result  from  the  first  division  of  the  fertilized  ovum,  two  cells  which  are 


• "Zona   pellucida 

— '  Nucleus 

;~  Spermatozoon 

— ~  Cytoplasm 


Head  of 

spermatozoon 
with  centrosome 


.  Female  pronucleus 


Male  pronucleus 


Male  pronucleus 
Female  pronucleus 


Chromosomes  of 
iBmale  pronucleus 


"^  Chromosomes  of 
male  pronucieus 


Centrosome 


,'  Chromosome  from 
*         female  pronucleus 


-•--..  Chromosome  from 
•"•/         male  pronucleus 


11 

\1  '*• ;  ,';Y.;.»viV-,-  --r- Centres 


FIG.  22. — Diagram  of  fertilization  of  the  ovum.     (The  somatic  number   of   chromosomes    is   4.) 

Boveri,  Bohm  and  i'on  Davidoff. 

apparently  exactly  alike  and  each  of  which  contains  exactly  the  same  amount  of 
male  and  of  female  chromosome  elements  (Fig.  22,  6). 

The  amphiaster  of  the  fertilized  ovum  appears  to  develop  as  in  ordinary 
mitosis.     As  to  the  origin  of  the  centrosomes,  however,  much  uncertainty  still 


FERTILIZATION.  37 

exists.  The  middle  piece  of  the  spermatozoon  always  enters  the  ovum  with  the 
head.  It  has  already  been  shown  (p.  24)  that  one  or  two  spermatid  centro- 
somes  take  part  in  the  formation  of  the  middle  piece.  Male  centrosome 
elements  are  therefore  undoubtedly  carried  into  the  ovum  in  the  middle  piece.  It 
is  equally  well  known,  for  some  forms  at  least,  that  the  centrosome  of  the  ovum 
disappears  just  after  the  extrusion  of  the  second  polar  body.  In  a  considerable 
number  of  forms  the  development  of  the  centrosome  of  the  fertilized  egg  from,  or 
in  close  relation  to  the  middle  piece  of  the  spermatozoon  has  been  observed. 
The  details  of  the  process  as  it  occurs  in  the  sea-urchin  have  been  care- 
fully described  by  Wilson.  In  cases  of  this  type  the  tail  of  the  spermato- 
zoon remains  outside  the  egg  while  the  head  and  middle  piece,  almost  im- 
mediately after  entering,  turn  completely  around  so  that  the  head  points  away 
from  the  female  pronucleus  (Fig.  23,  a).  An  aster  with  its  centrosomes  next 
appears,  developing  from,  or  in  very  close  relation  to  the  middle  piece.  The 
aster  and  sperm  nucleus  now  approach  the  female  pronucleus,  the  aster  leading 
and  its  rays  rapidly  extending.  On  or  before  reaching  the  female  pronucleus 
the  aster  divides  into  two  daughter  asters  (Fig.  23,  b)  which  separate  with  the 
formation  of  the  usual  central  spindle,  while  the  two  pronuclei  unite  in  the 
equatorial  plane  and  give  rise  to  the  chromosomes  of  the  cleavage  nucleus 
(Fig.  23,  c  and  d).  In  the  sea-urchin  the  polar  bodies  are  extruded  before  the 
entrance  of  the  spermatozoon.  In  cases  where  the  polar  bodies  are  not  ex- 
truded until  after  the  entrance  of  the  spermatozoon  (Ascaris,  Fig.  9)  the 
amphiaster  forms  while  waiting  for  their  extrusion,  the  nuclei  joining  sub- 
sequently. When  the  sperm  head  finds  the  polar  bodies  already  extruded, 
union  of  the  two  pronuclei  may  take  place  first,  followed  by  division  of  the 
centrosome  and  the  formation  of  the  amphiaster. 

The  coming  together  of  ovum  and  spermatozoon  is  apparently  determined 
largely  by  a  definite  attraction  on  the  part  of  the  ovum  toward  the  spermato- 
zoon. This  attraction  seems  to  be  chemical  in  nature  and  is  specific  for  germ 
cells  of  a  particular  species,  that  is,  ova  possess  attractive  powers  toward 
spermatozoa  of  the  same  species  only.  This  has  been  proved  in  some  of  the 
lower  forms  by  mixing  ova  and  spermatozoa  in  a  suitable  medium  with  the  re- 
sult that  the  spermatozoa  become  attached  to  the  membrane  of  the  ova  in  large 
numbers.  Spermatozoa  of  other  species  will  not,  however,  be  thus  attracted. 
That  this  attraction  is  not  dependent  upon  the  integrity  of  the  ovum  as  an 
organism  is  shown  by  the  fact  that  small  pieces  of  egg  cytoplasm  free  from 
nuclear  elements  exert  the  same  attractive  force,  so  that  spermatozoa  are  not 
only  attracted  to  them  but  will  actually  enter  them. 

Of  eggs  which  are  enclosed  by  a  distinct  membrane,  the  vitelline  membrane, 
some  (e.g.,  those  of  Amphibians  and  of  Mammals)  are  permeable  to  the 
spermatozoon  at  all  points;  others  have  a  definite  point  at  which  the  spermat- 


38 


TEXT-BOOK  OF  EMBRYOLOGY. 


ozoon  must  enter,  this  being  of  the  nature  of  a  channel  through  the  membrane 
— the  micropyle.     In  some  instances  a  little  cone-shaped  projection  from  the 


•.  •  *•*.•*.  e  •;.: .  i"  ^  ;• 

.:  •  _.0  '.  >  **.!•  */ 

•    •*.'  :#  • 


FIG.   23. — Fertilization  of  the  ovum  of  Thalassema.     Griffin, 
•j? ,  Male  pronucleus,    f,  female  pronucleus. 

surface  of  the  egg,  the  attraction  cone  (Fig.  22,  i),  either  precedes  or  imme- 
diately follows  the  attachment  of  the  spermatozoon  to  the  egg.  Instead  of  a 
projection  there  may  be  a  depression  at  the  point  of  entrance. 


FERTILIZATION. 


39 


There  seems  to  be  no  question  that  but  one  spermatozoon  has  to  do 
with  the  fertilization  of  a  particular  ovum.  In  Mammals  only  one  spermato- 
zoon normally  pierces  the  vitelline  membrane  although  several  may  penetrate 
the  zona  pellucida  (Fig.  22,  i)  to  the  perivitelline  space.  Should  more  than  one 
spermatozoon  enter  such  an  egg — as,  for  example,  in  pathological  polyspermy — 
the  result  is  an  irregular  formation  of  asters  and  polyasters  (Fig.  24)  and  the 
early  death  of  the  egg  either  before  or  soon  after  a  few  attempts  at  cleavage. 
In  some  Insects,  and  in  Selachians,  Reptiles  and  Birds,  a  number  of  sperma- 
tozoa normally  enter  an  ovum,  but  only  one  goes  on  to  form  a  male  pronucleus. 

The  ovum  thus  not  only  exerts  an  attractive  influence  toward  spermatozoa, 
but  it  apparently  exerts  this  influence  only  until  the  one  requisite  to  its  fertiliza- 
tion has  entered,  after  which  it  appears  able  to  protect  itself  against  the  further 
entrance  of  male  elements.  As  to  the  means  by  which  this  is  accomplished 
little  is  known,  although  several  theories  have  been  advanced.  It  may  be  that 


c 


FIG.   24. — Polyspermy  in  sea-urchin  eggs  treated  with  0.005  Per  cent-  nicotine  solution.     O.  and  R. 

Hertu'ig,  Wilson. 

B,  Showing  ten  sperm  nuclei,  three  of  which  have  conjugated  with  female  pronucleus.     C,  Later 
stage  showing  polyasters  formed  by  union  of  sperm  amphiasters. 

when  the  single  spermatozoon  necessary  to  accomplish  fertilization  has  entered 
the  ovum,  it  sets  up  within  the  ovum  such  changes  as  to  destroy  the  attractive 
powers  of  the  ovum  toward  other  spermatozoa,  or  as  even  to  prevent  their 
entrance.  In  the  case  of  eggs  where  the  spermatozoon  enters  through  a  micro- 
pyle,  it  has  been  suggested  that  the  tail  of  the  first  spermatozoon  remaining  in 
the  opening  might  effectually  block  the  entrance  to  other  spermatozoa;  or  the 
passage  of  the  first  spermatozoon  might  set  up  such  mechanical  or  chemical 
changes  in  the  canal  as  would  prevent  further  access.  In  most  cases  of  eggs 
which  have  no  vitelline  membrane  previous  to  fertilization,  such  a  membrane  is 
formed  immediately  after  the  entrance  of  the  first  spermatozoon,  a  natural 
inference  being  that  this  membrane  may  prevent  the  entrance  of  any  more 
spermatozoa.  Biologists,  however,  are  inclined  to  discredit  the  view  that  the 
fertilization  membrane  is  a  protection  against  polyspermy. 


40  TEXT-BOOK  OF  EMBRYOLOGY. 

Nothing  is  known  in  regard  to  fertilization  of  the  human  ovum.  It  has  been 
shown  that  in  some  of  the  lower  Mammals  fertilization  regularly  takes  place 
in  the  oviduct,  and  it  is  reasonable  to  assume  that  it  occurs  in  the  oviduct  in 
man.  That  spermatozoa  can  pass  into  and  even  all  the  way  through  the 
oviduct  is  proved  by  cases  of  tubal,  abdominal  and,  rarely,  ovarian  pregnan- 
cies. On  the  other  hand  Wyder  considers  the  uterus  as  the  normal  site  of 
fertilization,  and  some  other  gynecologists  say  that  fertilization  may  take 
place  in  the  uterus.  Waldeyer  also  concludes  that  fertilization  may  occur  in 
the  uterus. 

Significance  of  Fertilization.* 

Mitotic  cell  division  constitutes  the  wonderful  mechanism  by  which  not  only  the  con- 
tinuity of  life  but  also  the  maintainance  of  the  species  is  accomplished.  "From  an  a  priori 
point  of  view  there  is  no  reason  why,  barring  accidents,  cell  division  should  not  follow  cell 
division  in  endless  succession. ' '  And  it  is  probable  that  such  is  the  case  among  the  lower 
forms  of  animal  and  vegetable  life,  where  no  true  sexual  reproduction  occurs.  A  one-celled 
animal  or  plant  may  divide  and  produce  two  individuals;  each  of  these  two  may  produce 
two  more,  and  so  on  a d  infinitum.  "In  the  vast  majority  of  forms,  however,  the  series  of 
cell  divisions  tend  to  run  in  cycles  in  which  the  energy  of  division  comes  to  an  end  and  is 
restored  only  by  an  admixture  of  living  matter  from  another  cell." 

This  admixture  of  the  living  matter  of  tv,-o  cells  is  known  as  fertilization  and  is  the 
essential  feature  of  sexual  reproduction.  It  is  the  process  which  on  the  one  hand  restores 
to  the  cell  the  energy  necessary  to  continue  its  division  and  on  the  other  hand  accomplishes 
the  blending  of  two  independent  lines  of  descent. 

Certain  views  regarding  the  significance  of  fertilization  may  be  grouped  together  as  the 
rejuvenescence  theory.  The  earlier  embryologists  regarded  fertilization  as  "a  stimulus  given 
by  the  spermatozoon,  by  which  the  ovum  is  'animated'  and  made  capable  of  development." 
The  more  modern  "dynamic"  theorists  express  practically  the  same  conception.  They  hold 
that  protoplasm  tends  to  pass  gradually  into  a  state  of  equilibrium  in  which  activity  dimin- 
ishes, and  that  fertilization  restores  to  it  a  state  of  activity  through  the  admixture  of  protoplasm 
which  has  been  subjected  to  different  conditions. 

Certain  known  facts  tend  in  a  general  way  to  support  these  theories.  For  example, 
among  the  Protozoa  or  one-celled  animals,  a  long  series  of  cell  divisions  is  followed  by  con- 
jugation. In  conjugation  two  individuals  come  together  and  fuse  permanently,  or  inter- 
change substances  and  separate  again.  This  process  results  in  the  restoration  of  the  energy 
of  growth  and  division  and  a  new  life-cycle  is  begun.  Among  the  higher  animals  and 
plants  fertilization  is  always  necessary  for  the  initiation  of  a  new  life-cycle  with  its  subsequent 
cell  division  and  growth.  In  some  lower  forms,  however,  parthenogenesis  occurs  and  a  new 
life-cycle  is  initiated  without  the  union  of  cells  from  two  sexually  different  individuals.  It 
must  therefore  be  admitted  that  whether  or  not  the  tendency  toward  senescence  and  the  need 
of  fertilization  are  primary  attributes  of  living  matter  is  unknown. 

Parallel  with  the  rejuvenescence  theory  are  other  views  which  do  not  necessarily  oppose 
or  confirm  it.  One  view  in  particular  is  that  fertilization  is  in  some  way  concerned  with 
variations  in  the  individuals  of  a  species.  Brooks  and  Weismann  developed  the  hypothesis 
that  fertilization,  the  admixture  of  germ  plasms  from  two  individuals,  is  a  source  of  varia- 

*The  quotations  in  the  following  paragraphs  are  from  "The  Cell  in  Development  and 
Inheritance,"  by  E.  B.  Wilson. 


FERTILIZATION.  41 

tion — "a  conclusion  suggested  by  the  experience  of  practical  breeders  of  plants  and  animals." 
Weismann  himself  holds  that  the  need  of  fertilization  is  a  secondary  matter,  but  that  the 
admixture  of  different  germ  plasms  insures  the  mingling  and  renewal  of  variations. 

Spencer  and  Darwin,  on  the  other  hand,  believe  that  although  crossing  among  animals  or 
plants  may  lead  to  variability  within  certain  limits,  it  tends  in  the  long  run  to  hold  in  check 
any  wide  digression  from  a  norm  and  hold  the  species  true  to  type. 

PRACTICAL  SUGGESTIONS. 

Fertilization  of  the  ovum  may  be  observed  in  some  of  the  Invertebrates  and  makes  a 
wonderfully  interesting  process  to  observe  under  the  microscope.  In  the  sea-urchin,  for 
example,  whose  ova  are  relatively  small  and  transparent,  the  steps  may  be  followed  in  the 
living  objects.  The  mature  ova  are  removed  from  the  animal  and  placed  in  a  drop  of  sea- 
water  on  a  slide;  then  a  drop  of  seminal  fluid  mixed  with  sea -water  is  added.  A  cover-glass 
is  gently  applied,  and  it  is  best  to  place  a  thin  bit  of  glass  under  one  edge  to  prevent  crushing. 
The  following  phenomena  may  be  seen  under  a  fairly  high  power  lens :  In  less  than  a  minute 
a  vast  number  of  the  spermatozoa  are  clustered  around  each  egg.  Under  the  most  favorable 
conditions  one  of  these  spermatozoa  may  soon  be  seen  with  its  head  attached  to  the  ovum. 
The  head  penetrates  deeper  into  the  cytoplasm,  the  tail  becomes  motionless  and  finally 
invisible.  The  egg  nucleus  and  sperm  nucleus  then  seem  to  exert  a  mutual  attraction  and 
move  toward  each  other.  They  finally  come  in  contact  and  fuse,  the  product  of  their  fusion 
being  the  segmentation  nucleus.  The  whole  process  of  fertilization  has  not  occupied  more 
than  ten  minutes. 

In  Ascaris  the  behavior  of  the  sperm  nucleus  during  the  maturation  of  the  ovum  may  be 
inferred  from  the  different  stages  (see  "Practical  Suggestions,"  p.  33).  In  this  particular 
animal  the  two  pronuclei  do  not  actually  fuse  but  return  to  the  resting  stage  within  the  ovum 
and  then,  when  the  first  cleavage  is  about  to  occur,  break  up  into  their  respective  chromo- 
somes. 

References  for  Further  Study. 

CONKLIN,  E.  G.:  The  Embryology  of  Crepidula.     Jour,  of  Morphol,  Vol.  XIII,  1897. 

HARPER,  E.  H.:  The  Fertilization  and  Early  Development  of  the  Pigeon's  Egg.  Am. 
Jour,  of  Anat.,  Vol.  Ill,  No.  4,  1904. 

HERTWIG,  R.:  Eireife,  Befruchtung  u.  Furchungsprozess.  In  Hertwlg's  H andbuch  d. 
vergleich.  u.  experiment.  Entwickelungslehre  der  Wirbelliere,  Ed.  I,  Teil  I,  1903. 

KING,  H.  D.:  The  Maturation  and  Fertilization  of  the  Egg  of  Bufo  lentiginosus.  Jour, 
of  Morphol.,  Vol.  XVII,  1901. 

SOBOTTA,  J. :  Die  Befruchtung  u.  Furchung  des  Eies  der  Maus.  Arch.  }.  mik.  Anat.,  Bd. 
XLV,  1895. 

WILSON,  E.  B.:  The  Cell  in  Development  and  Inheritance,     zd  Ed.,  1900. 


CHAPTER  V. 


CLEAVAGE— (SEGMENTATION) . 

Following  fertilization  and  the  commingling  of  male  and  female  chromo- 
somes, there  occurs  the  usual  longitudinal  splitting  of  these  chromosomes  as  in 
ordinary  mitosis.  One-half  of  each  chromosome  now  passes  toward  each 
centrosome.  The  result  is  that  one-half  of  each  male  chromosome  and  one- 
half  of  each  female  chromosome  enter  into  the  formation  of  each  of  the  two 
new  daughter  nuclei  (Fig.  22,  4,  5  and  6).  The  phenomena  which  follow  are 
apparently  identical  with  those  of  ordinary  mitosis  and  result  in  two  similar 
daughter  cells.  Each  of  the  latter  next  undergoes  mitotic  division.  In  this 
manner  are  formed  four  cells,  eight  cells,  sixteen  cells,  and  so  on.  This  early 
multiplication  of  cells  which  follows  fertilization  is  known  as  cleavage  or 
segmentation  of  the  ovum,  the  cells  themselves  are  known  as  blastomeres  and  the 
cell  mass  as  the  morula. 

While  the  object  of  cleavage  and  its  results — the  proliferation  of  cells  from 
the  fertilized  ovum  and  subsequent  growth  and  development  of  the  embryo— 
also  the  general  features  of  the  process,  are  essentially  similar  in  all  eggs, 
marked  variations  in  details  of  cleavage  occur  in  eggs  of  different  forms, 
apparently  dependent  largely  upon  the  amount  of  yolk  present  and  its  distribu- 
tion within  the  egg.  (See  page  12.) 

We  distinguish  the  following  : 

FORMS  OF  CLEAVAGE. 

a.  Equal — e.g.,  alecithal  eggs  of  Sponges, 

Echinoderms,  some  Annelids, 
some  Crustaceans,  some  Mol- 
lusks,  Amphioxus,  Mammals. 

b.  Unequal — e.g.,     telolecithal    eggs    of 

Cycles  tomes,  Ganoid 
Fishes,  Amphibians;  usual 
type  in  Annelids  and  Mol- 
lusks. 

a.  Superficial — e.g.,  centrolecithal  eggs  of 

Arthropods. 

b.  Discoidal — e.g.,    telolecithal    eggs    of 

Cephalopods,     Bony    Fishes, 
Reptiles,  Birds. 
42 


Holoblastic  (complete  or  total) 


Meroblastic  (incomplete  or  partial) 


CLEAVAGE. 


43 


Holoblastic  Cleavage. 

(A)  EQUAL.— In  this  form  of  cleavage  the  entire  egg  divides  and  the  cells 
^suiting  from  the  early  cell  divisions  are  of  approximately  the  same  size.  One 
of  the  Echinoderms— Synapta— presents  a  beautiful  example  of  this,  the  simplest 
type  of  cleavage  (Fig.  25).  The  egg  of  Synapta  is  alecithal,  containing  very  little 
yolk.  The  first  cleavage  is  in  a  vertical  plane  at  right  angles  to  the  long  axis  of 
the  central  spindle  and  divides  the  egg  into  halves.  The  second  plane  of  cleavage 
is  also  vertical  but  is  at  right  angles  to  the  first  cleavage  plane  and  results  in  four 
equal  cells.  The  third  cleavage  plane  is  horizontal,  cutting  the  four  cells  result- 
ing from  the  second  cleavage  into  eight  equal  cells.  The  fourth  cleavage  is 


FIG.  25. — Cleavage  of  the  ovum   of   Synapta    (slightly   schematized).    Selenka,    Wilson. 
A-E,  Successive  cleavages  to  the  32-cell  stage.     F,  Blastula  of  128  cells. 

vertical,  the  fifth  horizontal  and  so  on,  regular  alternation  of  vertical  and  hori- 
zontal cleavage  planes  being  continued  through  the  ninth  set  of  divisions,  re- 
sulting in  512  cells.  At  this  point  gastrulation  begins  and  the  regularity  of  the 
cleavage  planes  is  lost.  Amphioxus  is  another  classical  example  of  equal 
holoblastic  cleavage,  being  classed  as  such,  although  after  the  third  cleavage  the 
cells  are  not  of  exactly  the  same  size.  In  Amphioxus  the  first  two  cleavage 
planes  are  vertical  and  at  right  angles,  as  in  Synapta.  The  third  cleavage  plane 
is  horizontal,  as  in  Synapta,  but  the  cells  lying  above  the  third  cleavage  plane  are 
smaller  than  those  lying  below  it.  The  eight-cell  stage  of  Amphioxus  thus 
presents  four  upper  smaller  cells  and  four  lower  larger  cells  (Fig.  26). 


44 


TEXT-BOOK  OF  EMBRYOLOGY. 


(B)  UNEQUAL. — A  good  example  of  this  form  of  cleavage  is  found  in  the 
common  frog's  egg  (Fig.  27).  This  egg  while  containing  little  yolk  when  com- 
pared with  such  eggs  as  those  of  the  fowl,  contains  much  more  yolk  than  does 
the  egg  of  Synapta  or  of  Amphioxus.  The  frog's  egg  being  a  telolecithal  egg, 
the  yolk  is  gathered  at  one  pole,  enabling  a  distinct  differentiation  to  be  made 
between  the  upper  darker  protoplasmic  or  animal  pole,  and  the  lower  lighter 
vegetative  pole  (Fig.  6).  The  cleavage  is  complete  but  the  cells  which  develop 
at  the  yolk  pole  are  much  larger  than  those  which  develop  at  the  protoplasmic 
pole.  The  first  and  second  cleavage  planes  are  as  in  Synapta  and  Amphioxus, 
vertical  and  at  right  angles  to  each  other.  Each  of  the  four  cells  which  result 
from  the  second  cleavage  in  the  frog  consists  of  a  small  upper  darker  proto- 
plasmic pole  and  of  a  larger  lower  lighter  yolk  pole  (Fig.  27,  A).  The 


Micromeres 


ml 


Macromeres 


FIG.  26. — Cleavage  of  the  ovum  of  Amphioxus.     Hatschek,  Bonnet. 
1-5,  Lateral  views  of  segmenting  cells;  6,  section  of  blastula. 

nuclear  elements  lying,  as  they  always  do,  within  the  protoplasmic  portion  of 
the  cell,  determine  the  next  cleavage  plane  which  is  horizontal  and  lies  nearer 
the  protoplasmic  ends  of  the  cells.  The  result  is  that  the  third  cleavage  gives 
rise  to  eight  cells,  four  of  which  are  small  protoplasmic  cells  lying  above  the 
line  of  cleavage,  while  the  other  four  are  large  yolk-containing  cells  which  lie 
below  the  line  of  cleavage  (Fig.  27,  A).  This  distinction  between  protoplasmic 
cells  and  yolk  cells  not  only  persists  but  tends  to  become  more  and  more  marked 
as  segmentation  proceeds,  and  it  soon  becomes  evident  that  the  cells  unencum- 
bered by  yolk  have  a  tendency  to  segment  more  rapidly  than  do  their  yolk- 
laden  brethren  (Fig.  27,  C,  D,  E,  F  and  G).  Thus,  while  the  fourth  cleav- 
age is  vertical  in  both  types  of  cells,  giving  rise  to  eight  upper  protoplasmic 
cells  and  the  same  number  of  lower  yolk  cells,  this  uniformity  of  number  per- 


CLEAVAGE. 


45 


sists  only  up  to  this  point,  while  beyond  this  point  the  protoplasmic  cells  in- 
crease in  number  much  more  rapidly  than  do  the  yolk  cells,  so  that  when  the 
protoplasmic  cells  number  128,  there  are  still  but  comparatively  few  yolk  cells. 
There  thus  result  in  total  unequal  cleavage  two  very  different  types  of  cells  each 
confined  to  its  own  part  of  the  segmenting  cell  mass. 


B 


H 


I 


FIG.  27. — Cleavage  of  the  frog's  egg.     Morgan. 

A,  Eight-cell  stage;  B,  beginning  of  sixteen-cell  stage;  C,  thirty-two-cell  stage;  D,  forty-eight-cell 
stage  (more  regular  than  usual);  E,  F,  G,  later  stages;  H,  I,  formation  of  blastopore. 

Meroblastic  Cleavage. 

(A)  SUPERFICIAL. — This  form  of  cleavage  is  seen  in  the  centrolecithal  eggs 
of  Arthropods.  These  eggs  (seep.  12)  consist  of  a  central  mass  of  nutritive 
yolk  surrounded  by  a  comparatively  thin  layer  of  protoplasm.  The  seg- 
mentation nucleus  lies  in  the  middle  of  the  nutritive  yolk  where  it  undergoes 
the  usual  mitotic  divisions.  The  resulting  daughter  nuclei  leave  the  central 
yolk  mass  and  pass  out  into  the  peripheral  layer  of  protoplasm  where  they  ap- 


46 


TEXT-BOOK  OF  EMBRYOLOGY. 


parently  determine  segmentation  of  the  protoplasm,  the  number  of  protoplasmic 
segments  corresponding  to  the  number  of  nuclei.  There  is  thus  formed  a 
superficial  layer  of  cells  (blastomeres)  enclosing  the  central  nutritive  yolk. 

(B)  DISCOIDAL. — This  type  of  cleavage  occurs  in  eggs  which  have  an 
excessive  amount  of  yolk  and  in  which  the  protoplasm  is  confined  to  a  small 
superficial  germ  disk.  The  telolecithal  ova  of  Birds  furnish  typical  examples 
of  this  form  of  cleavage.  The  first  cleavage  plane  is  vertical  and  divides  the 


c  d 

FIG.  28. — Cleavage  in  hen's  egg.     Coste.     Germinal  disk  and  part  of    yolk,  seen  from  above. 

protoplasmic  disk  into  halves.  The  second  cleavage  plane  is  also  vertical 
and  at  right  angles  to  the  first,  resulting  in  four  approximately  equal  cells 
(Fig.  28,  a).  The  third  cleavage  plane  is  also  vertical,  dividing  two  of  the 
four  cells  (Fig.  28,  b}.  The  germ  disk  at  the  end  of  the  third  cleavage  consists 
of  six  pyramidal  cells  lying  with  their  apices  together  in  the  center  of  the  germ 
disk,  their  bases  lying  peripherally  and  toward  the  yolk  mass.  They  are 
separated  from  one  another  at  the  surface,  but  are  still  continuous  below  and 


CLEAVAGE.  47 

peripherally  with  the  underlying  yolk  mass  and  consequently  with  each  other. 
The  analogy  between  this  condition  and  that  described  for  the  frog's  egg  is 
complete  with  the  one  exception  that  in  the  latter  the  cleavage  furrows  cut 
completely  through  the  yolk  cells  or  the  yolk-containing  portions  of  the  cells, 
while  in  the  bird's  egg  the  amount  of  yolk  is  so  great  that  the  cleavage  furrow 
merely  passes  a  short  distance  into  it  without  completely  dividing  it  into  seg- 
ments. The  fourth  cleavage  plane  is  tangential,  cutting  off  the  apices  of  the 
six  pyramidal  segments.  The  germ  disk  after  the  fourth  cleavage  thus  con- 
sists of  six  small  superficial  central  cells  and  six  larger  cells  which  surround 
the  small  cells  and  also  separate  the  latter  from  the  underlying  yolk.  From 
this  point  radial  and  tangential  cleavages  follow  each  other  without  any  sem- 
blance of  regularity.  The  result  is  a  mass  of  small  cells  lying  at  the  center  of 


FIG.  29. — From  a  vertical  section  through  the  germ  disk  of  a  fresh-laid  hen's  egg.     Duval,  Hertwjg. 
g.d.,  Upper  layer  of  germ  disk;  s.c.,  segmentation  cavity;  w.y.,  white  yolk  (see  Fig.  7);  y.s.,  lower 
layer  of  germ  disk  (yolk  cells,  merocytes). 

the  disk  and  surrounded  by  larger  cells  (Fig.  28,  c,  d).  The  smaller  cells  are 
completely  separated  from  the  underlying  yolk  while  the  larger  cells  are  for  a 
time  continuous  with  it  (Fig.  29). 

Comparing  the  unequal  holoblastic  cleavage  of  the  frog's  egg  with  discoidal 
meroblastic  cleavage  as  seen  in  the  eggs  of  Birds,  it  becomes  immediately 
evident  that  the  differences  between  them  are  explainable  entirely  by  reference 
to  the  greater  quantity  of  yolk  in  the  bird's  egg.  The  real  activity  of  segmenta- 
tion is  in  both  cases  confined  almost  wholly  to  the  protoplasm.  In  the  frog's 
egg  the  amount  of  yolk  present  is  sufficient  to  impede  segmentation  in  the 
larger  cells  but  not  to  prevent  it.  In  the  bird's  egg  the  amount  of  yolk  is  so 
great  that  it  cannot  be  made  to  undergo  complete  segmentation. 

Some  General  Features  of  Cleavage. 

Cleavage  in  Mammals. 

The  two  fundamental  laws  of  cleavage  as  formulated  by  Sachs  are: 
i.  That  each  cell  tends  to  divide  into  equal  parts. 

4 


48  TEXT-BOOK  OF  EMBRYOLOGY. 

2.  That  each  division  plane  tends  to  intersect  the  preceding  division  plane  at 
right  angles. 

The  first  of  these  laws  is  apparently  dependent  upon  the  fact  that  the 
nucleus  tends  to  occupy  the  center  of  the  protoplasmic  mass  which  is  to  undergo 
division.  In  the  case  of  a  spherical  cell  the  spindle  may  lie  in  any  diameter. 
In  case  one  axis  of  the  cell  is  longer  than  the  other  axis,  the  axis  of  the  spindle 
corresponds  to  the  long  diameter  of  th*e  cell.  When  the  cell  divides  the  division 
plane  always  bisects  the  spindle  perpendicularly  to  its  long  axis. 

Applying  these  laws  to  cleavage,  the  first  division  plane  bisects  the  long 
axis  of  the  first  division  spindle  at  right  angles,  the  axis  coinciding  with  the 
greatest  diameter  of  the  cytoplasmic  mass.  The  result  is  two  cells,  the  long 
axes  of  which  are  parallel  to  the  first  division  plane.  The  axes  of  the  mitotic 
spindles  in  these  two  daughter  cells,  coinciding  with  the  long  diameters  of  the 
cells,  are  therefore  at  right  angles  to  the  mitotic  spindle  of  the  mother  cell,  and 
the  second  division  plane  is  therefore  at  right  angles  to  the  first.  The  result  of 
the  second  division  is  four  cells  and  as  the  first  two  division  planes  were  vertical, 
the  long  axes  of  all  four  of  these  cells  are  vertical,  as  are  also  their  mitotic 
spindles.  The  third  division  plane  to  be  at  right  angles  to  these  spindles  must 
bisect  them  in  a  horizontal  plane.  The  third  cleavage  plane  is  therefore 
horizontal. 

Such  regular  cleavage  as  that  seen  in  Synapta  (p.  43)  in  which  after  the 
first  vertical  cleavage,  vertical  and  horizontal  cleavage  planes  alternate  with 
perfect  regularity  and  the  number  of  cells  is  exactly  doubled  at  each  cleavage 
through  the  ninth  cleavage  or  512  cells,  is  extremely  rare.  Thus  in  many  forms 
the  regular  doubling  of  the  number  of  cells  occurs  only  through  the  first  four  or 
five  cleavages.  This  is  exemplified  in  Nereis  where  regular  doubling  occurs 
through  the  fourth  cleavage,  giving  rise  to  sixteen  cells.  The  fifth  cleavage 
results  in  twenty  cells,  the  sixth  in  twenty-three,  the  numbers  at  successive 
cleavages  being  twenty-nine,  thirty-two,  thirty-seven,  thirty-eight,  forty-one, 
forty-two.  The  immediate  cause  of  such  irregularity  in  the  number  of  cells  is 
that  some  of  the  cells  divide  more  rapidly  than  others.  Thus  in  Nereis  after 
the  fourth  cleavage  not  all  the  cells  divide  at  any  one  time.  In  some  cases  the 
amount  of  yolk  present  in  the  cell  appears  to  influence  the  rapidity  of  division, 
the  cells  containing  the  greater  quantity  of  yolk  dividing  more  slowly  than  those 
containing  less  yolk.  While  this  is  generally  true,  exceptions  where  cells  con- 
taining much  yolk  divide  as  rapidly  as,  or  more  rapidly  than,  those  containing 
less,  prove  the  inadequacy  of  this  as  a  general  explanation  of  numerical  ir- 
regularity in  cleavage.  It  is  possible  that  in  many  instances,  at  any  rate,  the 
future  role  of  the  cell  as  regards  function  may  play  a  large  part  in  determining 
the  rapidity  of  its  segmentation.  After  the  forty-two-cell  stage  in  Nereis  the 
number  of  cells  at  each  successive  cleavage  is  indeterminate,  that  is,  it  varies 


CLEAVAGE.  49 

for  different  individuals.     In  other  species  this  variability  begins  much  earlier 
in  the  segmentation  series. 

In  addition  to  variations  in  the  number  and  size  of  the  cells  above  de- 
scribed, variations  also  occur  in  the  direction  of  the  cleavage  planes  and  in  the 
relations  of  the  resulting  cells.  In  all  eggs  except  centrolecithal,  the  first  two 
cleavage  planes  bisect  each  other  at  right  angles  through  the  protoplasmic  pole. 
Subsequent  cleavage  may  follow  one  of  three  types,  which  are  distinguished  as 
radial,  spiral  and  bilateral. 

Radial  cleavage  is  the  simple  type  of  cleavage  already  described  as  occurring 
in  Synapta  and  in  the  frog  (Figs.  25  and  27). 

Spiral  or  oblique  cleavage  occurs  chiefly  in  Worms  and  Mollusks.  The  differ- 
ence between  radial  and  spiral  cleavage  is  brought  out  in  the  second  division  in  the 
latter,  and  may  manifest  itself  in  the  telophase  of  the  first  division.  The  third 
cleavage  is  not  a  continuous  horizontal  plane  but  cuts  the  cells  in  such  a  manner 
that  the  four  lower  cells  have  a  position  as  if  rotated  one-half  cell,  usually  to  the 
right.  The  divisions  between  the  cells  of  the  lower  row  thus  alternate  with  those 
of  the  upper  row,  like  layers  of  bricks  in  a  wall.  The  next  horizontal  cleavage 
plane  is  also  oblique  but  is  at  right  angles  to  the  preceding  and  results  also  in 
alternation  of  all  the  cells.  This  regular  alternation  of  spiral  cleavage  planes 
may  continue  for  some  time,  but,  as  a  rule,  the  cleavage  soon  becomes  very 
irregular  and  there  is  usually  much  variation  in  size  of  the  blastomeres. 

In  the  bilateral  form  of  cleavage  seen  in  Tunicates  and  Cephalopods,  after 
the  first  cleavage,  the  cells  segment  symmetrically  on  each  side  of  the  first 
plane. 

In  some  forms  the  cleavage  appears  to  follow  definite  rules  as  regards  the 
number  of  cells  which  result  from  each  segmentation.  This  is  known  as  deter- 
minate cleavage.  In  other  cases,  after  a  number  of  divisions,  the  number  of 
cells  resulting  from  each  cleavage  is  indefinite,  that  is,  it  varies  for  each  indi- 
vidual. This  is  designated  indeterminate  cleavage. 

Reviewing  the  results  of  cleavage,  it  is  to  be  noted  that  in  every  case  there  is 
formed  a  larger  or  a  smaller  group  of  cells.  In  the  case  of  equal  holoblastic 
cleavage,  these  cells  are  all  of  the  same  or  of  nearly  the  same  size,  and  constitute 
what  is  known  as  the  morula  or  mulberry  mass  (Fig.  25,  E).  A  similar  condition 
obtains  in  unequal  holoblastic  cleavage  with  the  one  exception,  that  there  is 
a  marked  difference  in  the  size  of  the  cells  constituting  the  morula  (Fig.  27). 
In  superficial  meroblastic  cleavage  the  group  of  cells  forms  a  layer  enclosing  the 
central  yolk,  the  latter  being  unsegmented  but  containing  some  nuclei.  In 
discoidal  meroblastic  cleavage  the  group  of  cells  spreads  itself  over  a  limited 
superficial  area,  while  beneath  it  lies  the  large  mass  of  unsegmented  yolk,  con- 
taining, however,  some  nuclei  (Figs.  28  and  29). 

In  holoblastic  cleavage  the  blastomeres  in  the  interior  of  the  mass  become 


50  TEXT-BOOK  OF  EMBRYOLOGY. 

more  or  less  separated  during  segmentation,  a  cavity  thus  being  formed  within 
the  so-called  morula.  This  cavity  increases  in  size,  the  cells  being  pushed 
centrif  ugally  and,  the  embryo  soon  consists  of  a  layer  or  layers  of  cells  enclosing  a 
cavity,  the  segmentation  cavity.  The  entire  embryo  is  now  known  as  the  blastula. 
The  simplest  type  of  blastula  is  seen  in  Amphioxus,  where  it  consists  of  a 
nearly  spherical  segmentation  cavity  surrounded  by  a  single  layer  of  cells. 
Some  of  the  cells — those  wrhich  are  more  ventral  and  contain  the  larger 
amount  of  yolk — are  slightly  larger  than  others  (Fig.  26,  6). 

In  the  eggs  of  the  frog,  in  which  the  cells  resulting  from  segmentation  show 
greater  inequality  in  size  (due  to  difference  in  yolk  content),  the  segmenta- 
tion cavity  is  surrounded  by  several  layers  of  cells.  In  such  a  blastula  the  roof 
of  the  cavity  is  comparatively  thin,  being  composed  of  small  cells  containing 

Micromeres. 


Macromeres. 

FIG.  30. — From  a  sagittal  section  through  blastula  of  frog.     Bonnet, 
mz.,  Marginal  zone. 

little  yolk,  micromeres,  while  the  floor  of  the  cavity  is  thick,  being  composed 
of  large  yolk  cells,  macromeres.  So  thick  is  this  wall  of  the  vegetative  pole  of  the 
blastula  that  the  large  yolk  cells  extend  into  the  segmentation  cavity  compress- 
ing it  into  a  crescentic  cleft  (Fig.  30).  In  the  frog  the  roof  of  the  segmentation 
cavity  is  sharply  denned  from  the  floor,  due  to  the  fact  that  the  outer  layer  of 
cuboidal  roof  cells  is  densely  pigmented.  The  rather  sharply  defined  zone  of 
transition  between  pigmented  micromeres  and  nonpigmented  macromeres  is 
known  as  the  marginal  zone. 

In  discoidal  segmentation,  the  segmentation  cavity  is  a  mere  slit  between  the 
superficial  protoplasmic  cells  and  the  underlying  unsegmenting  yolk  with  its 
yolk  nuclei  (Fig.  29).  Comparing  it  with  unequal  holoblastic  cleavage,  these 
partially  divided  yolk  cells  which  form  the  floor  of  the  segmentation  cleft  in 


CLEAVAGE. 


51 


discoidal  cleavage  are  analogous  to  the  large  yolk  cells  which  form  the  floor  of 
the  segmentation  cavity  in  the  frog.     (Compare  Figs.  29  and  30.) 

In  the  mammalian  ovum,  as  in  the  other  cases  just  described,  segmentation 
leads  up  to  the  formation  of  a  solid  mass  of  cells — the  morula.     While  cleavage 


FIG.  31. — Four  stages  in  cleavage  of  the  ovum  of  the  mouse.    Sobotta 
Small  cell  marked  with  x  is  the  polar  body. 

here  is  of  the  holoblastic  equal  type,  the  irregularity  is  especially  marked.  In 
the  mouse,  for  example,  the  second  cleavage  is  complete  in  one  of  the  blasto- 
meres  before  it  has  begun  in  the  other,  so  that  a  three-celled  stage  results 


Subzonal 
space 

Morula 


FIG.  32. — Morula  of  rabbit,     van  Beneden. 

(Fig.  31).  Following  this  is  a  four-celled  stage.  From  this  time  on  cleavage 
continues  irregularly  until  a  solid  mass  is  formed,  as  in  the  lower  forms, 
which  is  composed  of  apparently  similar  cells  (Fig.  32). 

The  next  step  in  mammalian  development  is  a  differentiation  of  the  super- 


52 


TEXT-BOOK  OF  EMBRYOLOGY. 


ficial  layer  of  the  cells  of  the  morula.  The  result,  then,  is  a  single  surface  layer, 
the  covering  layer,  surrounding  a  central  mass  of  polygonal  cells  (Fig.  33,  a). 
This  solid  mass  of  cells  is  transformed  into  a  vesicle  by  vacuolization  of  some  of 
the  inner  cells  (Fig.  33)  and  the  confluence  of  these  vacuoles  to  form  a  cavity. 
The  mammalian  ovum  at  this  stage  thus  consists  of  two  groups  of  cells  and  a 
cavity,  an  outer  group  or  layer  of  cuboidal  cells,  the  outer  cell  layer  or  covering 
layer  (trophoderm} ,  forming  the  wall  of  the  cavity,  and  an  inner  group  of 


w 


FIG.  33. — Four  stages  in  the  development  of  the  bat.     van  Beneden. 

a,  Section  of  morula;  b,  section  of  later  stage  of  morula,  showing  differentiation  of  outer  layer  of 
cells;  c,  section  of  still  later  stage,  showing  vacuolization  of  central  cells;  d,  section  showing  outer 
layer  (trophoderm)  and  inner  cell  mass. 

polygonal  or  spheroidal  cells,  the  inner  cell  mass  which  at  one  point  is  attached 
to  the  outer  layer  of  cells  (Fig.  33,  d). 

The  mistake  must  not,  however,  be  made  of  considering  the  mammalian 
ovum  at  this  stage  as  a  true  blastula.  The  mammalian  ovum  apparently  does 
not  pass  through  any  true  blastula  stage.  Of  the  parts  just  described,  the 
inner  cell  mass  alone  is  comparable  to  the  blastoderm  of  birds,  while  the  cavity 
corresponds  not  to  the  segmentation  cavity  but  to  the  yolk  mass  of  meroblastic 
eggs.  The  vacuolization  of  the  cells  of  the  inner  cell  mass  would  thus  represent 
a  late  and  abortive  attempt  at  yolk  formation,  the  actual  nutritive  yolk  being 


CLEAVAGE.  53 

made  unnecessary,  since  the  attachment  of  the  ovum  to  the  walls  of  the  uterus 
provides  for  direct  parental  nutrition.  In  the  separation  of  the  cells  of  the 
morula  into  an  inner  cell  mass  and  an  outer  covering  layer  is  seen  the  earliest 
differentiation  into  cells  (inner  cell  mass),  which  are  destined  to  form  the 
embryo  proper,  and  cells  (outer  cells — covering  layer)  which  are  to  engage  in 
the  development  of  certain  accessory  structures. 

PRACTICAL  SUGGESTIONS. 

The  ova  of  the  star-fish  or  sea-urchin  afford  excellent  material  for  the  study  of  total 
(holoblastic)  equal  cleavage  up  to  and  including  the  blastula  and  gastrula  stages.  During  the 
breeding  season  for  these  animals  (late  in  June  or  early  in  July  in  the  latitude  of  New  York) 
the  ova  are  readily  obtained  and  easily  fertilized  under  artificial  conditions.  The  ova  are 
removed  and  placed  in  shallow  vessels  containing  sea-water.  The  seminal  fluid  is  mixed 
with  a  small  quantity  of  sea-water  and  some  of  the  mixture  is  added  to  the  water  containing 
the  ova.  Gentle  agitation  will  serve  to  disseminate  the  spermatozoa.  Fertilization  occurs 
within  half  an  hour  and  cleavage  follows  very  shortly.  A  few  of  the  ova  are  placed  on  a 
slide  and  watched  under  the  microscope  until  the  first  cleavage  is  nearly  complete  and  then 
any  desired  quantity  may  be  treated  as  follows:  Remove  the  ova  from  the  vessel  by  means 
of  a  pipette,  care  being  taken  not  to  take  up  any  more  water  than  is  absolutely  necessary. 
Eject  them  into  5  per  cent,  formalin  contained  in  a  slender,  cylindrical  bottle.  After  a 
few  minutes  (when  the  ova  have  settled  to  the  bottom)  it  is  best  to  change  the  formalin.  The 
ova  may  remain  in  the  formalin  indefinitely. 

The  later  stages  in  cleavage  may  be  determined  and  secured  in  the  same  manner.  The 
process  goes  on  rapidly  and  blastulae  will  appear  in  a  few  hours,  gastrulae  in  a  little  longer 
time. 

To  prepare  permanent  mounts,  proceed  as  follows: 

Alcohol,  30%,  50%,  70%,  an  hour  in  each  grade. 

Borax-carmin,  few  hours. 

Alcohol,  70%,  slightly  acidulated  with  HC1,  few  hours. 

Alcohol,  70%,  several  changes,  few  hours. 

Alcohol,  95%,  one  hour. 

Alcohol,  absolute,  one  hour. 

Xylol,  one  hour. 

Thin  xylol-damar,  indefinitely. 

Remove  some  of  the  ova  in  a  pipette,  place  on  a  slide  and  apply  a  cover-glass.  In  order 
to  prevent  crushing,  it  is  best  to  place  a  few  bits  of  broken  cover-glass  in  the  damar  on  the 
slide  before  applying  the  cover-glass. 

Eggs  of  the  common  frog  are  good  examples  of  total  unequal  cleavage.  The  ova  in 
various  stages  of  cleavage  can  be  procured  in  ponds  during  the  spring  and  preserved  indefi- 
nitely in  5  per  cent,  formalin.  A  hand  lens  or  even  the  naked  eye  will  be  sufficient  to  deter- 
mine the  earlier  stages  (two,  four,  eight  and  sixteen  cells).  For  closer  examination  a  few 
of  the  ova  may  be  placed  in  the  formalin  or  in  water  in  a  watch-glass.  The  cleavage  furrows 
on  the  surface  are  remarkably  clear. 

Permanent  preparations  of  a  number  of  stages  for  use  in  a  large  class  may  be  made  by 
removing  the  individual  ova,  each  with  its  gelatinous  capsule  still  intact,  from  the  general 
mass  and  placing  in  formalin  in  slender  test-tubes.  The  tubes  should  have  a  diameter  just 


54  TEXT-BOOK  OF  EMBRYOLOGY. 

small  enough  not  to  allow  the  eggs  to  slip  past  one  another.  In  this  way  the  stages  may  be 
kept  in  order,  and  the  tightly-  corked  tubes  may  be  handled  in  any  way  to  get  the  best  light 
on  the  eggs. 

References  for  Further  Study. 

ASSHETON,  R.:  The  Segmentation  of  the  Ovum  of  the  Sheep,  with  Observations  on  the 
Hypothesis  of  a  Hypoblastic  Origin  for  the  Trophoblast.  Quart,  Jour,  of  Mic.  Science, 
Vol.  XLI,  1898. 

BLOUNT,  M.:  The  Early  Development  of  the  Pigeon's  Egg,  with  Especial  Reference  to 
the  Supernumerary  Sperm  Nuclei,  the  Periblast  and  the  Germ  Wall.  Biolog.  Bull.,  Vol. 
XIII,  No.  5,  1907. 

CONKLIN,  E.  G.:  Karyokinesis  and  Cytokinesis.  Jour.  Acad.  Nat.  Sci.  0}  Philadelphia, 
Vol.  XII,  1902. 

CONKLIN,  E.  G.:  The  Embryology  of  Crepidula.     Jour,  of  MorphoL,  Vol.  XIII,  1897. 

EYCLESHYMER,  A.  C.:  The  Early  Development  of  Amblystoma,  with  Observations  on 
Some  Other  Vertebrates.  Jour,  of  MorphoL,  Vol.  X,  1895. 

HARPER,  E.  H.:  The  Fertilization  and  Early  Development  of  the  Pigeon's  Egg.  Am. 
Jour,  of  Anal.,  Vol.  Ill,  No.  4,  1904. 

HATSCHEK,  B.:  Studien  iiber  Entwickelung  des  Amphioxus.  Arbeiten  aus  dem  zool. 
Instil,  zu  Wien,  Bd.  IV,  1881. 

HERTWIG,  R.:  Eireife,  Befruchtung  u.  Furchungsprozess.  In  Hertwig's  Handbuch  d. 
vergleich  u.  experiment.  Entwickelungslehre  der  Wirbeltiere,  Bd.  I,  Teil  I,  1903. 

LILLIE,  F.  R.:  The  Development  of  the  Chick.     New  York,  1908. 

MORGAN,  T.  H.:  The  Development  of  the  Frog's  Egg.     New  York,  1897. 

SOBOTTA,  J.:  Die  Befruchtung  u.  Furchung  des  Eies  der  Maus.  Arch.  f.  mik.  Anat., 
Bd.  XLV,  1895. 

VAN  BENEDEN,  E.:  Recherches  sur  les  premiers  stades  du  developpement  du  Murin 
(Vespertilio  murinus).  Anat.  Anz.,  Bd.  XVI,  1899. 

WILSON,  E.  B.:  The  Cell  in  Development  and  Inheritance.     2d  Ed.,  1900. 


CHAPTER  VI. 

GERM  LAYERS.* 

THE  TWO  PRIMARY  GERM  LAYERS— FORMATION  OF  THE  GASTRULA. 
Gastrulation  in  Amphioxus. 

The  changes  which  immediately  follow  the  formation  of  the  blastula  can  be 
observed  in  their  simplest  form  in  Amphioxus,  where,  it  will  be  remembered, 
the  blastula  is  a  hollow  sphere  the  wall  of  which  consists  of  a  single  layer  of  cells 
which  enclose  the  segmentation  cavity  (Fig.  26,6).  Gastrulation  begins  by  a 
flattening  of  the  ventral  wall  of  the  blastula  (Fig.  34,  A).  This  is  followed  by 
a  folding  in  or  invagination  of  the  yolk  cells  which  form  the  ventral  wall  (Fig. 
34,  B).  These  cells  press  upward  into  the  segmentation  cavity  which  they  soon 
completely  obliterate,  and  come  to  lie  immediately  beneath  and  in  contact  with 
the  smaller  cells  which  had  formed  the  roof  of  the  cavity  (Fig.  34,  C). 

The  gastrula,  as  the  embryo  is  now  called,  thus  consists  of  two  layers  of  cells 
which  lie  in  close  apposition  and  enclose  the  new  cavity,  the  archenteron  (ccelen- 
teron — primitive  gut)  formed  by  the  invagination  (Fig.  34,  C  and  £>).  This 
cavity  remains  open  externally,  the  opening  being  known  as  the  blastopore 
(Fig.  34,  C  and  Z>).  These  two  layers  of  cells  which  form  the  wall  of  the  gastrula 
are  the  primary  germ  layers.  The  outer  layer  is  known  as  the  ectoderm  or 
epiblast,  the  inner  layer  as  the  entoderm  or  hypoblast.  As  seen  by  reference  to 
Fig.  34,  C  and  D,  the  two  primary  germ  layers  are  directly  continuous  with  each 
other  at  the  blastopore. 

The  most  significant  feature  of  the  transformation  of  the  blastula  into  the 
gastrula  is  that  whereas  in  the  blastula  all  the  cells  are  essentially  similar, 
differing  if  at  all  only  in  the  amount  of  yolk  contained,  in  the  gastrula  two  dis- 
tinct types  of  cells  are  recognizable.  The  cells  of  the  outer  layer  differ  from 
those  of  the  inner  layer  both  structurally  and  functionally.  Thus  in  some  of  the 
lowest  forms  the  gastrula  stage  is  the  adult  stage.  In  such  the  outer  cells  are 
protective,  react  to  external  stimuli,  develop  cilia  which  determine  locomotion, 
etc.  The  inner  cells,  on  the  other  hand,  are  more  especially  concerned  with 
nutrition,  absorbing  food,  and  giving  off  waste  products.  Von  Baer's  apprecia- 

*For  many  of  the  ideas  contained  in  this  chapter,  especially  the  correlation  of  gastrulation  and 
the  formation  of  the  mesoderm  in  different  forms,  the  writers  are  indebted  to  Bonnet's  excellent  de- 
scription in  his  "  Lehrbuch  der  Entwickelungsgeschichte." 

The  homologizing  of  gastrulation  in  the  different  forms  has  been  found  the  most  satisfactory 
method  of  teaching  the  subject.  At  the  same  time  it  must  be  admitted  that  some  of  the  correlations 
are  not  based  on  actual  observations. 

55 


56 


TEXT-BOOK  OF  EMBRYOLOGY. 


tion  of  the  significance  of  this  first  cell  differentiation  is  evidenced  by  the  fact 
that  he  designated  the  two  primary  germ  layers  the  "primitive  organs"  of  the 
body. 

It  should  be  noted  that  with  the  completion  of  gastrulation  certain  important 
landmarks  in  adult  topography  have  been  established.     Thus  the  animal 


Segmentation  cavity 


Micromeres 


Segmentation  cavity 


Macromeres 


Invagination 


D 

Archenteron  Anterior  lip  of  blastopore 


Blastopore 

Post,  lip  of 
blastopore 


Ectoderm    Entoderm  Ectoderm  Entoderm 

FIG.  34. — Gastrulation  in  Amphioxus.     Hatschek,  Bonnet. 

(micromere)  pole  is  always  the  dorsum;  the  vegetative  (macromere)  pole 
always  the  ventrum;  the  blastopore,  being  always  caudal,  differentiates  the 
tail  end  from  the  head  end  of  the  embryo. 

Gastrulation  in  Amphibians. 

This  is  modified  as  compared  with  gastrulation  in  Amphioxus  by  the 
presence  of  a  greater  amount  of  yolk.  A  clear  understanding  of  the  modifica- 
tions which  this  increased  yolk  content  causes  in  the  gastrulation  of  Amphibians, 


GERM   LAYERS.  57 

as  well  as  of  Reptiles  and  Birds,  is  essential  to  a  proper  appreciation  of  the 
process  in  Mammals. 

Recalling  the  amphibian  blastula  (p.  50),  it  will  be  remembered  that  its 
roof  was  formed  of  smaller  protoplasmic  cells  (micromeres)  while  its  floor  con- 
sisted of  a  mass  of  yolk  cells  which  encroached  upon  the  segmentation  cavity 


Micromeres 


—   Macromeres 


FIG.  35. — Vertical  section  through  blastula  of  Triton.     Hertwig. 

(Fig.  30).  The  zone  of  union  between  the  two  kinds  of  cells  is  known  as  the 
marginal  zone.  The  simplest  type  of  amphibian  gastrulation,  and  the  type 
thus  most  easily  compared  with  gastrulation  in  Amphioxus,  is  exemplified  by 
the  water  salamander — Triton  taeniatus.  (Compare  Figs.  34  and  35.) 


Ectoderm 
Entoderm 


Anterior  lip  of  blastopore 

Blastopore 

Posterior  lip  of  blastopore 

Yolk  cells 
(entoderm) 


Segmenta-  __ 
tion  cavity 


FIG.  36. — Vertical  section  through  embryo  of  Triton,  showing  beginning  of  gastrulation.     Hertwig. 

In  Triton,  a  slight  groove  or  furrow  appearing  along  a  portion  of  the  marginal 
zone  marks  the  blastopore  and  the  beginning  of  gastrulation.  The  upper  lip 
of  this  groove  is  formed  by  the  smaller  protoplasmic  cells,  the  lower  by  the  large 
yolk  cells  (Fig.  36).  The  groove  next  deepens,  the  micromeres  growing  in  at 
the  dorsal  lip  to  form  the  roof  of  the  archenteron,  while  the  yolk  cells  are  carried 


58  TEXT-BOOK  OF  EMBRYOLOGY. 

over  the  ventral  lip  to  form  the  floor.  The  invagination  cleft  which  thus  be- 
comes the  archenteron  is  at  first  small  as  compared  with  the  segmentation  cavity, 
but  rapidly  increases  in  size,  until  as  in  Amphioxus,  the  earlier  cavity  is  finally 
completely  obliterated  (Fig.  37).  Coincident  with  the  carrying  of  the  yolk 
cells  into  the  interior  of  the  vesicle  and  the  obliteration  of  the  segmentation 
cavity,  proliferation  of  the  micromeres  carries  them  completely  around  the  yolk 
cells,  so  that  the  entire  surface  of  the  gastrula  is  formed  of  small  cells  (Fig.  37). 
The  amphibian  gastrula  thus  consists  of  a  central  cavity,  the  archenteron, 
communicating  with  the  exterior  by  means  of  a  small  opening,  the  blastopore, 
the  roof  of  the  cavity  being  formed  by  two  or  more  layers  of  small  cells,  the 
floor  by.  the  mass  of  large  yolk  cells.  The  outer  layer  of  cells  completely  sur- 
rounds the  yolk  cells  except  at  the  blastopore,  and  constitutes  the  ectoderm 
(Fig.  37).  The  inner  layer  or  entoderm  is  distinct  only  in  the  roof  of  the  cavity. 
Laterally  its  cells  pass  over  without  any  distinct  demarcation  into  the  mass  of 

Ectoderm 

Entoderm  (protentoderm) 

Archenteron 

-  Yolk  cells  (yolk  entoderm) 
Peristomal  mesoderm 

Yolk  plug 

Posterior  lip  of  blastopore 

Peristomal 
mesoderm 


FIG.  37. — Vertical  section  through  gastrula  of  Triton.     Hertwig. 

yolk  cells  which  form  the  floor  of  the  cavity.  As  the  ectoderm  forms  a  com- 
plete outer  layer,  the  only  point  at  which  the  yolk  cells  now  appear  externally  is 
the  blastopore,  into  which  they  project  as  the  yolk  plug  (Fig.  37). 

It  is  possible  in  the  amphibian  gastrula  to  make  the  distinction  between  the 
entoderm  of  the  roof  which  has  grown  in  from  the  surface  and  is  continuous 
with  the  surface  ectoderm,  and  the  entoderm  of  the  floor  which  is  formed  of  yolk 
cells.  By  those  who  make  this  distinction,  the  former  is  called  the  protentoderm, 
the  latter  the  yolk  entoderm  (Fig.  37). 

In  the  case  of  the  common  frog,  the  eggs  of  which  are  so  easily  obtained 
that  they  furnish  most  satisfactory  subjects  for  study,  gastrulation  is  somewhat 
less  simple  than  in  Triton.  As  already  noted  (p.  50)  the  demarcation  between 
micromeres  and  macromeres  is  in  the  frog  very  distinct,  owing  to  the  dark  pig- 
mentation of  the  former.  This  is  shown  in  Fig.  30,  as  is  also  the  fact  that  the 
roof  of  the  segmentation  cavity  consists  of  a  surface  layer  of  strongly  pig- 


GERM  LAYERS.  59 

mented  cells,  and  beneath  this  a  layer  of  less  pigmented  cells.  Fig.  38  shows 
the  beginning  of  gastrulation,  being  a  slightly  earlier  stage  than  the  Triton 
gastrula  (Fig.  36). 

In  the  frog  (also  in  the  toad  and  salamander)  a  modification  of  the  comple- 
tion of  gastrulation  occurs,  which,  while  apparently  unimportant,  is  considered 
by  some  investigators  as  having  significance  in  the  interpretation  of  gastrulation 
in  higher  forms,  especially  in  Mammals.  It  is  illustrated  in  Fig.  39.  The 
wedge-shaped  mass  of  yolk  cells  is  pushed  in  front  of  the  invagination  cleft  and 
carried  around  dorsally  just  beneath  the  ectoderm  (Fig.  39,  6).  This  is  met  in 
the  medial  dorsal  plane  by  yolk  cells  which  have  grown  up  from  the  floor  of  the 
segmentation  cavity  on  the  opposite  side  (Fig.  39,  c).  What  was  the  segmenta- 

Cells  with 
much  pigment 

^&  B^ — 

Micromeres 


Macromeres  • 

\ 

\ 

Invagination  (blastopore) 
FIG.  38. — From  sagittal  section  of  blastula  of  frog,  showing  beginning  of  gastrulation.     Bonnet. 

tion  cavity  thus  becomes  divided  into  a  cleft  beneath  the  ectoderm  and  a  cavity 
surrounded  by  yolk  cells.  The  cavity  is  designated  by  Bonnet  the  "  Erganzungs- 
hohle"  or  "completion  cavity"  (Fig.  39,  c,  d,  e).  With  continued  enlargement 
of  the  invagination  cavity,  the  cleft-like  remains  of  the  segmentation  cavity 
beneath  the  ectoderm  becomes  obliterated  and  the  "completion  cavity"  becomes 
pressed  ventrally.  The  wall  between  the  latter  and  the  invagination  cavity 
thins  and  finally  ruptures  so  that  the  two  cavities  become  one. 

It  thus  happens  that  at  one  stage  there  are  three  cavities  (Fig.  39,  d) — (i) 
the  slit-like  remains  of  the  segmentation  cavity,  (2)  the  invagination  cavity  and 
(3)  the  so-called  "completion  cavity."  The  remains  of  the  segmentation 
cavity  is  seen  by  reference  to  the  figures  to  lie  between  the  ectoderm  externally 
and  the  protentoderm  and  yolk  entoderm  internally.  The  invagination  cavity 


60 


TEXT-BOOK  OF  EMBRYOLOGY. 


is  limited  mainly  by  protentoderm,  the  "completion  cavity"  by  yolk  entoderm. 
The  breaking  of  the  partition  between  the  invagination  cavity  and  the  "com- 
pletion cavity"  results  in  the  formation  of  the  archenteron  proper  or  primitive 
gut,  which  is  thus  lined  partly  by  protentoderm  and  partly  by  yolk  ento- 


Ectoderm 


"Wedge" 


Blastopore 


Yolk  plug 


Yolk  plug 

Post,  lip  of 
blastopore 

FIG.  39. — Successive  stages  of  gastrulation  in  the  frog,  showing  especially  the  formation  of  the 
protentoderm,  yolk  entoderm  and  "completion  cavity."  Schultze,  Bonnet.  Com.  pi.,  "Completion 
plate." 

derm,  the  two  being  from  now  on  called  simply  entoderm.  The  somewhat 
thickened  area  of  yolk  cells  at  the  junction  of  the  protentoderm  and  yolk 
entoderm  is  designated  by  Bonnet,  the  "Erganzungsplatte"  or  "completion 
plate"  (Fig.  39,  d,  e). 


GERM   LAYERS. 


61 


Gastrulation  in  Reptiles  and  Birds. 

This  is  further  modified  by  the  still  greater  increase  in  yolk,  yet  retains 
sufficient  similarity  to  the  process  in  Amphibians  and  Amphioxus  to  allow  of 
comparison. 


FIG.  40. — Surface  view  of  blastoderm  of  snake.     Hcrtwig.     Blastopore  is  represented  by  dark 
transverse  band  near  lower  side  of  figure. 

In  the  types  of  gastrulation  thus  far  described — in  Amphioxus,  Triton  and 
the  frog — the  entire  egg  is  involved  in  segmentation  and  gastrulation.  Up 
through  these  forms  there  is  a  progressive  increase  in  the  amount  of  yolk,  which 


Blastoderm 


Embryonic  disk 


Anterior  lip 

Posterior  lip 
of  blastopore 


Blastopore 
(crescentic  groove) 


FIG.  41. — Surface  view  of  embryonic  disk  of  turtle  (Emys  taurica).     Bonnet. 
X,  The  lighter  shading  represents  the  opacity  due  to  the  growth  of  the  protentoderm  (see  Fig.  42). 

in  Triton  and  still  more  in  the  frog  was  seen  to  modify  the  gastrulation  process. 
In  the  reptilian  and  the  avian  ovum  there  is  a  much  greater  increase  in  yolk 
content,  the  segmentation  being  confined  to  the  germ  disk  and  to  a  small  part  of 


62 


TEXT-BOOK  OF  EMBRYOLOGY. 


the  underlying  yolk  (p.  46).     Just  as  cleavage  in  Reptiles   and   Birds  was 
modified  by  the  presence  of  the  large  unsegmenting  yolk  mass,  so,  for  the  same 


Ectoderm  of  embryonic  disk 


Blastopore 


Ectoderm 


Yolk  entoderm 
Blastopore 


Ectoderm 


'Completion  Protentoderm  Yolk  entoderm 

plate" 


Blastopore  * 


Peristomal  mesoderm 


"Completion  plate"  Yolk  entoderm 

FIG.  42. — From  medial  vertical  sections  through  embryonic  disk  of  lizard,  showing  five  successive 
stages  in  gastrulation.     Wenckebach,  Bonnet. 

reason,  is  gastrulation  quite  modified,  as  compared  with  the  simple  process  seen 
in  Amphioxus.  At  the  same  time,  however,  it  is  possible  to  correlate  the  reptil- 
ian and  avian  gastrulation  with  gastrulation  in  the  lower  forms. 


GERM   LAYERS. 


63 


Sfrf  ""  Area  apaca 
—  Area  pellucida 


Blastopore 
(crescentic 
groove) 


It  will  be  remembered  that  in  the  discoidal  cleavage  of  Birds  the  blastula 
consists  of  a  cleft-like  segmentation  cavity,  the  roof  of  which  is  formed  by  the 
proliferating  micromeres  constituting  the  germ  disk,  while  the  floor  is  formed  by 
the  partially  segmenting  yolk  (Fig.  29).  The  former  corresponds  to  the  micro- 
meres  of  the  blastula  roof  in  Amphioxus  and  Amphibians,  the  latter  to  the 
underlying  yolk  cells.  (Compare  Figs.  26,  6,  30  and  29.) 

In  Reptiles  the  beginning  of  gastrulation  is 
evidenced  by  the  appearance  of  an  opacity  just  in 
front  of  what  may  now  be  designated  the  posterior 
margin  of  the  disk  (Fig.  40).  This  is  due  to  more 
rapid  proliferation  of  cells  at  this  point.  The 
opacity  soon  sho\vs  a  depression  or  groove  which 
more  or  less  sharply  defines  the  posterior  margin 

of  the  disk.     It  varies  in  shape  in  different  Rep-     ,  FlG-  43— Surface  view  of  blasto- 
derm   of    unmcubated    hen  s   egg. 
tiles.     It  is  frequently  crescent-shaped  and  has    Hertwig. 

been  called  the  crescentic  groove  (Fig.  41).     This 

groove  is  the  blastopore,  and  corresponds  to  the  blastoporic  invagina- 
tions  of  Amphioxus,  Triton  and  the  frog.  Soon  after  the  formation  of  the 
crescentic  groove,  there  appears  in  front  of  it  an  oval  opacity  which  extends 
forward  in  the  medial  line  (Fig.  41).  This  opacity  is  due  to  growth  of  cells 
forward  from  the  blastopore  under  the  surface  cells  as  seen  in  Fig.  42  which 
shows  the  progress  of  the  invagination  in  the  lizard.  These  figures  should  be 

compared  with  Figs.  34,  36  and  37, 
showing  the  stages  of  gastrulation  in 
Amphioxus  and  Triton,  and  especially 
with  Figs.  38  and  39  showing  gastrula- 
tion in  the  frog. 

In  Fig.  42,  i,  the  blastopore  is  seen 
as  a  distinct  invagination.  As  in  the 
frog  (Fig.  39)  the  invagination  pushes 
in  front  of  it  a  wredge-shaped  mass  of 
cells  which  extends  forward  under  the 
outer  layer.  These  cells  are  the  pro- 
tentoderm.  They  form  the  roof  and, 
with  the  underlying  yolk  entoderm,  the 
floor  of  the  new  invagination  cavity 

(Fig.  42,  2).  As  they  extend  forward  they  meet  with  a  thickened  part  of 
the  yolk  entoderm,  the  "Erganzungsplatte"  or  "completion  plate"  (Fig.  42, 
2,  3,  4  and  5;  compare  Fig.  39).  There  are  thus  present  at  this  stage,  just 
as  in  the  frog,  three  cavities,  (i)  the  slit-like  remains  of  the  segmentation 
cavity,  (2)  the  invagination  cavity  and  (3)  the  "completion  cavity."  Also 
5 


p.b.  a.b. 


arc.  ec.  en. 


FIG.  44. — From  vertical  longitudinal  section 
through  germ  disk  of  siskin,  showing  beginning 
of  gastrulation.  Duval. 

a.b.,  Anterior  lip  of  blastopore;  arc.,  archen- 
teron;  ec.,  ectoderm;  en.,  entoderm;  p.b.,  posterior 
lip  of  blastopore;  y.,  white  yolk;  y.c.,  yolk  cells 
(merocytes). 


64 


TEXT-BOOK  OF  EMBRYOLOGY. 


as  in  the  frog  (Fig.  39),  by  a  breaking  through  of  the  two  layers — the  pro- 
tentoderm  and  the  yolk  entoderm — which  separate  the  invagination  cavity 
from  the  "completion  cavity"  in  Fig.  42,  2,  the  two  cavities  are  united  to  form 
the  archenteron  or  primitive  gut  (Fig.  42,  3,  4  and  5).  The  single-layered  germ 
disk  has  thus  become  transformed  into  a  two-layered  disk  consisting  of  an  outer 
(upper)  layer — the  ectoderm — and  an  inner  (lower)  layer — the  entoderm 
(protentoderm). 

In  Birds  the  gastrula  is  formed  in  a  manner  quite  comparable  with  its  forma- 
tion in  Reptiles.  Taking  the  hen's  egg  as  an  example,  it  will  be  remembered 
that  the  entire  segmentation  area  is  confined  to  the  germ  disk,  and  that  this  con- 
sists of  a  superficial  layer  (roof  of  segmentation  cavity)  of  small  well  defined 
cells  (micromeres)  beneath  which  is  the  cleft-like  segmentation  cavity,  while  the 
floor  of  this  cavity  is  formed  of  incompletely  segmented  yolk  (Fig.  29).  The 
beginning  of  gastrulation  is  marked  by  the  appearance  of  a  crescentic  bar  near 
the  posterior  margin  of  the  disk.  This  bar  is  due  to  more  rapid  proliferation 
of  the  cells  in  this  region,  and  in  it  there  appears  the  crescentic  groove  or  blasto- 

y.c.  a.b.    arc.         ec.    en. 


FIG.  45. — From  vertical  longitudinal  section  through  two-layered  germ  disk  of  nightingale.     Herfwig. 
a.b.,  anterior  lip  of  blastopore;  arc.,  archenteron;  ec.,  ectoderm;  en.,  entoderm  (protentoderm);  y.c.t 
yolk  cells  (merocytes.) 

pore  (Fig.  43).  Just  as  described  in  lower  forms,  especially  Reptiles,  the 
micromeres  invaginate  or  fold  under  at  this  point  and  grow  forward  as  th( 
protentoderm,  and  roof  in  the  new  cavity  formed  by  the  invagination  (Fig.  44). 
The  single-layered  germ  disk  is  thus  transformed  into  a  two-layered  disk  con- 
sisting of  an  outer  (upper)  layer — the  ectoderm — and  an  inner  (lo\ver)  layer  - 
the  entoderm  (protentoderm).  The  protentoderm  in  a  sense  replaces  the 
original  layer  of  yolk  cells  in  the  area  where  the  invagination  occurs;  the  original 
outer  layer  (micromeres)  becomes  the  ectoderm,  except  that  portion  which  is 
invaginated  to  form  the  protentoderm  (Fig.  45).  This  process  is  comparable 
with  the  disappearance  of  the  yolk  entoderm  in  Reptiles  (Fig.  42).  At  the  same 
time  the  segmentation  cavity  is  obliterated  and  the  new  cavity — invagination 
cavity — which  is  in  communication  with  the  exterior,  appears  beneath  the 
protentoderm.  (Compare  Figs.  42  and  45.) 

Under  the  central  portion  of  the  germ  disk  the  yolk  becomes  liquefied, 
while  at  the  margin  of  the  disk  it  continues  to  segment  and  give  rise  to  large 
nucleated  cells — the  yolk  entoderm.  This  is  known  as  the  area  of  supplemental 


GERM   LAYERS. 


65 


cleavage  and  apparently  corresponds  to  the  "Erganzungsplatte"  or  "com- 
pletion plate"  described  in  lower  forms  (p.  60;  see  also  Figs.  39  and  42). 
The  germ  disk  continues  to  spread  out  over  the  yolk  and  at  the  same  time  the 
area  of  liquifying  yolk  increases.  The  portion  of  the  disk  above  the  liquified 
yolk  appears  translucent  on  surface  view  and  is  known  as  the  area  pellucida; 
the  more  peripheral  part  of  the  disk  is  less  transparent,  being  more  closely 
attached  to  the  unchanged  yolk,  and  is  known  as  the  area  opaca. 


Area  opaca 


Hensen's  node 


Primitive  streak" 


Area  pellucida 
"Completion  plate' 
Head  process 


Primitive  groove 


Post,  lip  of 
blastopore 


FIG.  46. — Surface  view  of  embryonic  disk  of  chick.     Bonnet. 

There  next  appears  in  front  of  the  crescentic  groove  and  extending  from  its 
middle  point  forward  in  the  medial  line,  a  linear  opacity  which  is  known  as  the 
primitive  streak  (Fig.  46).  This  ends  anteriorly  in  a  knob-like  expansion — 
Hensen's  node.  According  to  Duval,  Hertwig,  Bonnet  and  others,  the  primi- 
tive streak  is  formed  in  the  following  manner.  A  notch  or  indentation  appears 
in  the  anterior  lip  of  the  transverse  blastoporic  slit  (Figs.  43  and  47,  A).  As 


Area  opaca 
Area  pellucida 

•  Primitive  streak 


-  Area  pellucida 
r-  Area  opaca 
•-  Primitive  streak 


Blastopore 
(crescentic  groove) 


of   blastoderms    of    Haliplana,  showing  formation  of  primitive  streak. 
Schaitinsland. 


A  B 

FIG.  47. — Surface    views 

the  germ  disk  is  constantly  spreading  in  all  directions,  if  the  apex  of  this  notch 
remains  fixed,  the  extension  of  the  disk  posteriorly  must  result  in  a  drawing  out 
of  the  notch  into  a  longitudinal  slit  (Fig.  47,  B).  In  other  words,  the  horns  of 
the  crescentic  slit  are  pushed  together  to  form  a  longitudinal  slit.  And  as  the 
two  lips  of  the  slit  come  together  they  fuse,  and  the  line  of  fusion  is  marked  by  a 
shallow  groove,  the  primitive  groove.  At  the  anterior  end  of  the  slit  in  the  region 


66 


TEXT-BOOK  OF  EMBRYOLOGY. 


of  Hensen's  node,  there  is  a  small  area  where  fusion  does  not  occur,  thus  leaving 
a  small  opening  which  communicates  with  the  cavity  of  the  primitive  gut.  Since 
the  primitive  groove  is  formed  from  the  original  crescentic  slit,  and  the  original 
crescentic  slit  is  the  blastopore,  the  primitive  groove  may  be  considered  as  a 
modified  blastopore  in  which  the  only  opening  is  at  Hensen's  node.  The 
primitive  groove  lies  in  the  medial  line  of  the  primitive  streak;  and  since  the 
primitive  groove  is  a  modified  blastopore,  the  two  primary  germ  layers  are  fused 


ec.   en.  arc. 


FIG.  48. — From  transverse  section  through  Hensen's  node — germ  disk  of  chick  of  2  to  6  hours'  incu- 
bation.    Diival.    For  lettering  see  FIG.  49. 

at  the  lips  of  the  primitive  groove  (Figs.  48  and  49).  To  this  fusion  is  due  the 
opacity  which  constitutes  the  primitive  streak  as  seen  from  the  surface  (Fig.  46). 
After  the  formation  of  the  primitive  groove  and  streak  there  is  no  longer  any 
specially  marked  definition  of  the  posterior  margin  of  the  germ  disk,  the  entire 
circumference  having  a  uniform  demarcation. 

Very  soon  after  the  formation  of  the  primitive  streak  a  new  opacity  appears 
which  extends  forward  in  the  medial  line  from  Hensen's  node  (anterior  lip  of 
the  blastopore).  This  is  known  as  the  head  process,  or  "primitive  intestinal 


en.   ec.   f.g. 


r^-^^^s^^^^m^w^s§^ ^5%>& 
mi^^&^^^^f^^lMM^m^m 


FIG.  49. — From  transverse  section  through  primitive  groove — germ  disk  of  chick  of  2  to  6  hours'  incu- 
bation.    Duval. 

arc.,  Archenteron;  ec.,  ectoderm;  en.,  entoderm;   l.b.,  lip   of  blastopore;  p.g.,  primitive  groove;  y., 
yolk;  y.p.,  yolk  plug. 

cord"  (Bonnet)  (Fig.  50).  This  new  opacity  is  due  to  growth  of  cells  under  the 
ectoderm,  the  cells  constituting  the  protentoderm.  As  a  matter  of  fact,  this 
formation  of  the  protentoderm  is  a  further  extension  of  that  same  process 
which  began  with  the  crescentic  groove  (blastopore)  invagination  and  continued 
during  the  transformation  of  the  crescentic  groove  into  the  primitive  streak 
(still  the  blastopore).  Consequently  this  whole  process  from  the  formation  of 
the  crescentic  groove  up  entirely  through  the  formation  of  the  protentoderm,  is 


GERM  LAYERS. 


67 


homologous  with  the  simpler  protentoderm  formation  from  the  crescentic 
groove  (blastopore)  in  Reptiles.  (Compare  Fig.  51  with  Fig.  42.)  As  the 
protentoderm  grows  forward  in  the  medial  line  it  apparently  replaces  the  yolk 
entoderm,  so  that  the  roof  of  the  new  cavity — the  archenteron — is  formed  of 
protentoderm.  The  area  where  the  protentoderm  fuses  with  the  yolk  entoderm 
is,  as  in  Reptiles,  the  "completion  plate." 

The  only  real  difference  between  gastrulation  in  Reptiles  and  in  Birds  is 
that  in  Birds  the  crescentic  groove  (original  blastopore)  becomes  transformed 
into  the  primitive  groove  which  remains  open  only  at  its  anterior  end  (Hensen's 
node), while  in  Reptiles  the  blastopore  may  be  of  any  form,  crescentic,  round,  oval, 
etc.,  but  does  not  usually  present  a  longitudinal  linear  appearance.  Thus  in  the 
latter  case  the  primitive  intestinal  invagination  (the  head  process,  "primitive 


" 
Area  pellucida .    

•  "Completion  plate" 
-Head  process 

ry  folds 
Hensen's  node. 

Primitive  streak 


FIG.  50. — Surface  view  of  chick  blastoderm.     Bonnet. 

intestinal  cord  ")  grows  forward  from  the  original  point  of  invagination  near  the 
posterior  margin  of  the  disk. 

Gastrulation  in  Mammals. 

Reference  to  the  description  of  segmentation  in  the  mammalian  ovum  and 
its  peculiarities  (p.  51)  makes  it  evident  that  these  peculiarities  must  deter- 
mine further  modifications  in  the  development  of  the  germ  disk  as  compared 
with  lower  forms.  It  will  be  remembered  that  segmentation  in  the  mamma- 
lian ovum  had  been  carried  to  the  differentiation  of  two  kinds  of  cells  (p.  52), 
an  outer  cell  layer  (trophoderm)  and  an  inner  cell  mass  (Fig.  33).  In  lower 
forms  the  first  cell  differentiation  came  with  the  formation  of  the  two  primary 
germ  layers,  the  ectoderm  and  the  entoderm,  and  these  with  the  enclosed  cavity 
constituted  the  gastrula.  The  first  cell  differentiation  in  Mammals  has,  how- 
ever, an  entirely  different  significance,  the  trophoderm  having  nothing  to 
do  with  the  formation  of  the  embryo  but  being  destined  to  give  rise  to  extra- 
embrvonic  structures.  It  is  the  cells  of  the  inner  cell  mass  or  embryonal  bud 


68 


TEXT-BOOK  OF  EMBRYOLOGY. 


BE) 


8   Tn 


which  give  rise  to  the  embryonic  structures  proper.  In 
other  words,  the  inner  cell  mass  alone  is  the  anlage  of 
the  embryo  and  this  at  this  stage  shows  no  differentiation 
into  germ  layers  (Fig.  33). 

The  initial  step  in  the  formation  of  the  two  primary 
germ  layers  in  the  mammalian  ovum  is  the  differentia- 
tion and  splitting  off  of  the  deeper  cells  of  the  inner 
cell  mass  (Fig.  52,  a).  These  cells  are  the  primitive 
entoderm  and,  as  a  single  layer,  soon  extend  around 
the  vesicle  until  they  completely  line  it.  They  lie  in 
apposition  to  the  cells  of  the  trophoderm  except  where 
separated  from  them  by  the  remaining  cells  of  the  inner 
cell  mass.  While  the  primitive  entoderm  is  extending 
around  the  vesicle,  vacuolization  of  the  more  superficial 
cells  of  the  inner  cell  mass  takes  place  (Fig.  52,  b)  and 
results  in  the  formation  of  a  cavity  between  the  over- 
lying trophoderm  and  the  still  remaining  cells  of  the 
inner  cell  mass.  This  cavity  is  known  as  the  amniotic 
cavity  (Fig.  52,  c).  Its  roof  is  formed  by  the  tropho- 
derm, while  its  floor  is  formed  by  the  remaining  cells 
of  the  inner  cell  mass,  which  have  now  become  arranged 
in  a  distinct  layer  and  constitute  the  embryonic  disk 
(Fig.  52,  c).  The  latter  lies  directly  upon  the  primary 
entoderm  and  constitutes  the  surface  layer  of  the 
embryo — the  ectoderm.  Thus  at  this  stage  of  develop- 
ment, the  roof  of  the  amniotic  cavity  is  composed  of 
cells  which  are  to  give  rise  to  extraembryonic  structures, 
or  envelopes,  wrhile  the  floor  is  composed  of  the  two- 
layered  embryo  now  consisting  of  ectoderm  and  ento- 
derm. Those  investigators  who  attempt  to  homologize 
the  early  differentiation  of  cells  in  Mammals  and  in 
lower  forms,  consider  this  first  formed  entoderm  in 
Mammals  as  identical  with  the  yolk  entoderm  of  lower 
forms  and  so  designate  it,  although  it  does  not  consist 
of  yolk  cells.  The  protentoderm  is  formed  later  (p.  70). 

Considering  as  a  specific  example  gastrulation  in 
the  dog,  it  is  to  be  noted  that  just  before  gastrulation 
begins,  the  embryonic  disk  of  the  dog  is  essentially 
similar  to  that  of  the  bat  which  has  been  described 
(see  above),  with  the  exception  that  in  the  dog  the 
embryonic  disk  is  not  roofed  in  by  the  amnion.  At 


GERM   LAYERS. 


69 


the  stage  corresponding  to  Fig.  52,  c,  the  embryonic  disk  of  the  dog  presents  on 
surface  view  a  uniform  appearance. 

The  first  differentiation  noticeable  in  the  disk  is  an  opacity  at  what  now 
becomes  defined  as  the  posterior  margin  of  the  disk  (Fig.  53).     As  the  em- 


FIG.  52. — Sections   of  blastodermic  vesicle   of  bat,  showing  (a)   formation  of  the  entoderm  and 
(b  and  c)  of  the  amniotic  cavity,     van  Beneden. 

bryonic  disk  increases  in  size  a  linear  opacity  appears  extending  from  the 
opacity  at  the  posterior  margin  of  the  disk  forward  in  the  medial  line  to  a  point 
somewhat  anterior  to  the  center  of  the  disk.  The  appearance  (Fig.  53)  is 
strikingly  similar  to  that  of  the  chick  at  the  same  stage  (Fig.  46).  The  posterior 
opacity  corresponds  to  the  crescentic  groove,  the  linear  opacity  to  the  primitive 


70  TEXT-BOOK  OF  EMBRYOLOGY. 

streak,  its  anterior  club-shaped  end  to  Hensen's  node.  If  we  assume  the  same 
transformation  of  the  crescentic  groove  into  the  primitive  groove,  the  two  to- 
gether corresponding  to  the  blastopore,  the  condition  is  quite  analogous  to  that 
in  the  chick  (p.  65). 

At  a  slightly  later  stage  than  shown  in  Fig.  53,  a  new  opacity  appears  ex- 
tending forward  in  the  medial  line  from  Hensen's  node  (Fig.  54,  a).  This  is 
the  head  process,  and  may  be  considered  as  homologous  with  the  head  process  in 
the  chick.  (Compare  Fig.  54,  a,  with  Fig.  50.)  The  opacity  is  due  to  a  plate 
or  cord  of  cells  which  grows  from  the  region  of  Hensen's  node  forward  under  the 
surface  layer  of  cells  (ectoderm)  (Fig.  55).  On  the  assumption  that  Hensen's 


Embryonic  disk  • — ;'t~* 

Hensen's  node  ^l''"l^fB  mb&&&~   $3 

^'^"^aai^BK  ^K?v.  V.* 


FIG.  53. — Embryonic  disk  of  dog.     Bonnet.     The  letters  and  figures  on  the  right   (Si-S4)  indicate 

planes  of  sections  shown  in  Fig.  75. 

node  is  the  anterior  lip  of  the  blastopore,  this  plate  of  cells  may  possibly  be  con- 
sidered as  homologous  with  the  invaginated  cells  which  form  the  protentoderm 
in  Reptiles  and  Birds.  (Compare  Figs.  42,  51  and  55.)  Consequently,  since 
the  protentoderm  in  the  lower  forms  wras  designated  the  "primitive  intestinal 
cord"  (Urdarmstrang) ,  so  in  Mammals  this  invaginated  cord  of  cells  maybe 
called  the  "primitive  intestinal  cord"  (protentoderm)  (Fig.  54). 

In  Reptiles  it  has  been  seen  that  as  the  protentoderm  grows  forward  under 
the  surface  layer  (ectoderm)  the  yolk  entoderm  for  some  distance  disappears, 
and  the  protentoderm  fuses  with  the  remaining  yolk  entoderm  in  an  area 
known  as  the  completion  plate  (Fig.  42).  In  the  chick  also  it  has  been  stated 
that  a  similar  process  occurs  (p.  66).  In  Mammals  the  yolk  entoderm,  which 


GERM  LAYERS. 


71 


Embryonic  disk 
Hensen's  node 


Primitive  streak  • 

and  groove   « 

Embryonic  disk  _ 


Completion  plate 

f  Head  process 

.  Prim.  int.  cord 
(protentoderm) 


>  Mesoderm 


Ectoderm 


Yolk  entoderm 

Ectoderm 


Mesoderm 


Mesoderm 


Completion  plate 

Medullary  folds 


r-  .&i$$ 


^^^^^^^^^  rnmitive  groove 

f*«^^*****^#f««^;*jy^^^ffirarjtyi3..        j     ..Vi'iJ*/***'' 

'**..^  ^^imm*t**£  *^.* 


S< 


Mesoderm 


Yolk  entoderm 


Post,  end  of  prim,  streak 


Mesoderm 


Yolk  entoderm 


FIG.  54. — Surface  view  of  embryonic  disk  of  dog  and  transverse  sections  of  same.     Bonnet, 
a,  Disk  somewhat  further  advanced  than  that  in  Fig.  53;  the  letters  and  figures  (Sr-Sr)  indicate  planes 
of  sections  in  b.     m.  gr.,  medullary  groove. 


72 


TEXT-BOOK  OF  EMBRYOLOGY. 


was  present  from  the  time  of  its  differentiation  from  the  inner  cell-mass  (Fig.  52), 
apparently  disappears  or  is  replaced  by  the  protentoderm,  as  the  latter  grows 
forward  under  the  ectoderm  and  finally  the  protentoderm  becomes  continuous 
at  its  anterior  border  with  the  yolk  entoderm  that  remains.  The  area  wrhere  the 
two  become  continuous  is  the  "completion  plate"  (Fig.  55). 

The  disappearance  of  the  yolk  entoderm,  or  its  replacement  by  protentoderm, 
occurs,  however,  only  in  a  linear  area;  that  is,  the  protentoderm  grows  forward 
only  as  a  narrow  band  of  cells  which  replaces  a  correspondingly  narrow  band  of 


Mesoderm    Blastopore 


Embrvonic  disk 


Ectoderm  Mesoderm 


Yolk  entoderm  Chordal  plate  Completion  plate 

FIG.  55. — Medial  section  of  germ  disk  of  bat.     van  Beneden. 

yolk  entoderm.  And  since  this  strip  of  protentoderm  is  destined  to  give  rise  to 
the  notochord,  it  is  sometimes  known  as  the  "chordal  plate"  (Fig.  54,  S3). 
From  the  manner  of  formation  of  the  "chordal  plate,"  it  is  continuous  along 
each  side  with  the  yolk  entoderm  (Fig.  54,  S2). 

No  human  ovum  showing  gastrulation  has  been  observed.  What  is  known 
of  the  formation  of  the  germ  layers  in  man  is  discussed  on  p.  89. 

FORMATION  OF  THE  MIDDLE  GERM  LAYER— MESODERM. 

Mesoderm  Formation  in  Amphioxus.— In  such  a  simple  type  as  Amphi- 
oxus  the  formation  of  the  middle  germ  layer  is  readily  observed  and  there  is 
consequently  no  question  as  to  the  manner  in  which  it  arises.  In  higher  forms, 
however,  the  origin  of  the  mesoderm  has  been  and  still  continues  to  be  one  of 
the  most  difficult  of  embryological  problems. 

In  the  two-layered  Amphioxus  gastrula  the  mesoderm  first  appears  as  two 
symmetrical  evaginations  of  the  entoderm  which  push  out  dorso-laterally  from 
the  archenteron  (Fig.  56,  a).  That  part  of  the  entoderm  which  lies  between  the 
two  mesodermic  evaginations  is  composed  of  somewhat  higher  cells  than  those 
of  the  developing  mesoderm  and  constitutes  the  anlage  of  the  notochord  (chorda). 
The  lips  of  the  mesodermic  evaginations  next  come  together  (Fig.  56,  b)  in  such  a 
manner  that  the  mesoderm  becomes  completely  separated  from  the  archenteron 
(Fig.  56,  c).  While  this  separation  is  taking  place,  the  mesodermic  evaginations 
divide  transversely  into  a  number  of  segments  which  lie  on  each  side  of  the 
medial  line  and  are  known  as  the  mesodermic  somites — primitive  segments 
(Fig.  57).  Meanwhile,  the  chorda  anlage  is  being  transformed  into  the  chorda 


GERM   LAYERS. 


73 


itself.  This  transformation  is  initiated  by  an  evagination  dorsalward  of  the 
entodermic  cells  which  lie  between  the  two  mesodermic  evaginations  (Fig.  56,  c), 
these  cells  soon  becoming  constricted  off  as  the  solid  cord  of  cells  which  consti- 
tute the  notochord  (Fig.  56,  d).  With  the  separation  of  the  chorda,  the  remain- 
ing entoderm  unites  across  the  medial  line  and  becomes  the  epithelium  (en- 
toderm)  of  the  primitive  intestine.  The  formation  of  the  mesodermic  somites 
begins  near  the  middle  of  the  embryo  and  proceeds  caudally.  There  is  thus  at 
this  stage  a  row  of  somites  on  each  side  of  the  medial  line,  the  number  of  somites 


Notochord 


Entoderm 


Parietal 
mesoderm 
Visceral 
mesoderm 

Intestine 
Entoderm 


FIG.  56. — From  transverse  sections  through  Amphioxus  embryos,  showing  successive  stages  in  for- 
mation of  mesoderm,  neural  tube  and  notochord.     Bonnet. 

increasing  by  constant  differentiation  and  pushing  forward  of  more  segments 
(somites)  from  the  caudal  unsegmented  mesoderm  (Fig.  57). 

While  the  above  described  changes  have  been  taking  place,  those  ectodermic 
cells  which  lie  along  the  dorsal  medial  line  become  higher  and  form  the  bottom 
of  a  shallow  longitudinal  groove.  This  is  known  as  the  neural  groove,  while  the 
folds  which  bound  the  groove  on  each  side  are  known  as  the  neural  folds  (Fig. 
56,  a).  From  the  crests  of  the  folds  the  remaining  lower  ectodermic  cells  grow 
across  and  meet  in  the  medial  line  thus  forming  the  surface  ectoderm  (Fig.  56, 
b  and  c).  The  neural  groove  next  deepens,  the  neural  folds  bending  dorsally 


74 


TEXT-BOOK  OF  EMBRYOLOGY. 


and  toward  the  medial  line  where  they  finally  meet,  thus  converting  the  groove 
into  a  closed  canal  or  tube,  the  neural  tube  (Fig.  56,  d;  see  Chap.  XVII).  As  the 
ectoderm  grows  over  the  neural  groove  and  as  the  latter  becomes  transformed 
into  the  neural  tube,  there  remains  anteriorly  an  opening  from  the  exterior  into 


Anterior  (cephalic)  end 


Epidermis 
(ectoderm) 


Entoderm 


Archenteron 


Posterior  (caudal)  end 

FIG.  57. — From  horizontal  section  through  Amphioxus  embryo  with  5  primitive  segments;  seen  from 

dorsal  side.     Hatschek. 

The  communication  between  the  cavities  of  the  primitive  segments  (ccclom)  and  the  archenteron 
can  be  seen  in  the  last  4  segments. 

the  neural  tube.  This  is  known  as  the  neuropore  (Fig.  58).  Caudally,  the  neural 
groove  extends  over  the  region  of  the  blastopore  and  as  the  groove  closes  over  to 
form  the  neural  tube,  it  embraces  the  blastopore  which  now  becomes  closed 


Neuropore 

Primitive  segment   — 
Ccelom   (myocoel) 

Intestine 


Epidermis  (ectoderm) 
Neural  tube 


Anterior    \  lip  of 
Posterior  J  blastopore 

Unsegmented 
mesoderm 


FIG.  58. — From  vertical  section  through  Amphioxus  embryo  with  5  primitive  segments.     Hatschek. 

externally  but  opens  into  the  neural  tube.  This  opening,  which  thus  connects 
the  neural  tube  with  the  intestine,  is  known  as  the  neurenteric  canal  (Fig.  58), 
and  it  is  a  rather  remarkable  fact  that  while  giving  rise  to  no  adult  organ,  it  is 
found  without  exception  in  all  Vertebrates  which  have  been  studied. 


GERM  LAYERS.  75 

The  mesodermic  somites  meanwhile  extend  their  edges  ventrally  between 
the  ectoderm  and  the  entoderm  until  they  meet  and  fuse  in  the  midventral  line 
(Figs.  56,  d  and  59).  A  transverse  constriction  next  appears  which  cuts  off  the 
ventral  extension.  The  latter  is  known  as  the  lateral  plate,  while  the  remaining 
dorsal  part  is  still  designated  the  primitive  segment.  (Compare  Fig.  56,  d,  with 
Fig-  59)- 

The  primitive  segments  retain  their  segmental   character.     The  lateral 

plates,  on  the  other  hand,  do  not  retain  their  segmented  condition  but  fuse,  their 

cavities  uniting  to  form  the  primitive  body  cavity  or  ccelom,  which  is  the  anlage 

of  the  large  serous  cavities  of  the  adult.     The  outer  part  of  the  lateral  plate  or 

» 

Neural  tube 

^  Notochord 

Epidermis  (ectoderm) 

'  Primitive  segment 
Muscle  plate 

Cutis  plate 
Ccelom 

Primitive  segment ..  _^.  '-^11  ^  Coelom 

\l8       ffiU-l/  rt^Bm   I 

Intestine 


Splanchnocoel 

Parietal  mesoderm ". 

"lat.  plate 
Entoderm  • ^T"^fil<$^€^/  M      ~  Visceral  mesoderm  J 


Ventral        Subintestinal 
mesentery  vein 

FlG.  59. — Diagram  to  show  differentiation  of  primitive  segment  into  muscle  plate  (myotome)  and 
cutis  plate  and  relation  of  myocoel  and  splanchnocoel.     Bonnet.     Compare  with  Fig.  56,  d. 

parietal  mesoderm,  with  the  adjacent  ectoderm,  forms  the  somatopleure  (Fig.  59). 
The  inner  layer  of  the  lateral  plate,  the  visceral  mesoderm,  with  the  adjacent 
entoderm,  forms  the  splanchnopleure  (Fig.  59). 

At  the  caudal  end  of  the  embryo,  just  in  front  of  the  neurenteric  canal,  there 
exists  at  this  stage  an  area  where  the  germ  layers  have  not  become  differentiated 
to  form  special  structures.  In  this  area,  cell  proliferation  is  especially  active  and 
from  it  cells  are  derived  for  the  completion  of  the  neutral  tube,  chorda,  somites, 
intestine,  etc.  By  this  means  the  growth  of  the  embryo  in  length  is  provided 
for  (Figs.  57  and  58). 

The  Amphioxus  embryo  at  this  stage  thus  consists  of: 

1.  Ectoderm. — Surface  ectoderm  and  neural  tube. 

2.  Mesoderm. — Somites;  parietal  mesoderm  and  visceral  mesoderm 

enclosing  the  ccelom. 

3.  Entoderm. — Chorda  and  wall  of  primitive  intestine. 


76 


TEXT-BOOK  OF  EMBRYOLOGY. 


Mesoderm  Formation  in  Amphibians. — In  Amphibians  the  formation  of 
the  mesoderm  is,  like  gastrulation,  modified  by  the  presence  of  many  large  yolk 
cells.  Taking  for  an  example  the  water  salamander  (Triton),  which  furnishes 


Blastopore 


Ectoderm 
Parietal  mesoderm 

Visceral  mesoderm 


Entoderm 


Primitive  gut 
FIG.  60. — From  transverse  section  through  Triton  embryo  at  region  of  blastopore.     Hert-wig. 

perhaps  the  simplest  type  of  mesoderm  formation  in  Amphibians,  only  in  the 
region  of  the  blastopore  docs  the  mesoderm  formation  conform  at  all  closely  to 
that  of  Amphioxus.  In  this  region  the  middle  germ  layer  is  seen  to  consist  of 
two  lateral  evaginations  which  push  out  between  the  entoderm  and  ectoderm, 

Notochord  anlage        Neural  plate 


Parietal  mesoderm 
Visceral  mesoderm 


FIG.  61. — From  transverse  section  through  Triton  embryo  in  front  of  blastopore.     Hertwig, 

each  containing  a  cavity,  the  primitive  body  cavity  (Fig.  60).  More  cranially 
the  mesoderm  grows  out  laterally  between  the  entoderm  and  ectoderm,  not  as 
two  hollow  evaginations,  but  as  solid  plates  of  cells  which  only  later  separate  into 
two  layers  and  enclose  the  primitive  body  cavity  (Fig.  61).  Hertwig  considers 


GERM  LAYERS. 


77 


mesoderm  formation  in  Triton  entirely  analogous  to  its  formation  in  Amphioxus, 
the  solid  plate  of  cells  being  really  two  layers  enclosing  the  body  cavity,  but 
pressed  together  by  the  large  amount  of  yolk.  Although  the  mesoderm  de- 
veloped in  the  region  of  the  blastopore  and  that  which  originates  more  cranially 
are  continuous  in  front  of  the  blastopore,  it  is  convenient  to  designate  the 
former  the  peristomal,  the  latter  the  gastral  mesoderm. 

The  separation  of  the  mesoderm  into  a  dorsal  segmented  part  and  a  ventral 
unsegmented  part  containing  the  body  cavity;  the  formation  of  the  notochord 
between  the  two  lateral  plates  of  mesoderm  by  a  constricting  off  of  cells  from  the 
entoderm;  the  closure  of  the  primitive  intestine  beneath  the  notochord;  the 
development  of  the  neural  groove  and  folds  with  their  final  closure  to  form  the 
neural  tube;  and  the  extension  of  ectoderm  over  their  surface  to  form  the  surface 
ectoderm  (epidermis),  are  processes  quite  similar  to  the  formation  of  the  same 


Myocoel 


Neural 
tube 


Ccelom 


Notochord 


Primitive  segment 


Parietal  ) 

>  mesoderm 
Visceral  J 


Yoll 

(entoderm) 


FIG.  62. — From  transverse  section  through  dorsal  part  of  Triton  embryo.     Hertrwig. 


structures  in  Amphioxus  (Fig.  62).  Also  as  in  Amphioxus,  the  differentia- 
tion of  these  structures  is  more  advanced  cranially  and  gradually  extends 
caudally  where  for  some  time  there  exists  a  growth  area  in  which  they  are  not  as 
yet  differentiated. 

In  the  frog  the  formation  of  the  mesoderm  is  sufficiently  different  from 
Amphioxus  and  Triton  to  make  its  correlation  somewhat  difficult.  In  the  frog 
apparently  all  trace  of  mesodermic  Pagination  is  lost.  Taking  a  transverse 
section  through  the  frog's  gastrula  at  a  stage  when  the  blastopore  is  still  circular 
and  widely  open  (Fig.  39),  the  mesoderm  is  seen  as  a  flat  plate  of  cells  which 
blends  in  the  medial  line  with  the  protentoderm  and  ventrally  with  the  yoke 
entoderm  (p.  78,  Fig.  63).  The  mesoderm  has  here  arisen  apparently  by  a 
splitting  off  of  a  layer  of  cells  from  the  protentoderm,  the  remaining  cells  of  the 
protentoderm  forming  the  roof  of  the  primitive  gut.  Beginning  at  the  sides,  the 


78 


TEXT-BOOK  OF  EMBRYOLOGY. 


separation  of  the  mesoderm  extends  dorsally  to  the  chorda  and  ventrally,  as 
indicated  by  arrows  in  Fig.  63,  splitting  off  the  superficial  cells  of  the  yolk 
entoderm  until  the  mesoderm  becomes  completely  separated  from  the  yolk  cells. 
On  each  side  of  the  notochord  the  mesoderm  shows  a  shallow  longitudinal  groove 
(Fig.  64)  which  has  been  interpreted  by  some  as  the  homologue  of  the  meso- 
dermic  evagination  of  Amphioxus.  This  groove  does  not  persist,  however,  and 
has  nothing  to  do  with  the  formation  of  the  body  cavity.  The  latter  in  the  frog 
results  not  from  evagination  but  from  a  splitting  of  the  originally  solid  mesoder- 
mic  plates.  It  is  to  be  noted,  however,  that  while  the  ccelom  does  not  originate 
as  an  evagination  from,  and  is  never  connected  with,  the  primitive  intestine, 
the  mesoderm  itself  consists  of  cells  which  have  split  off  from  the  wall  of  the 

Chorda  anlage 


Mesoderm  — 
Protentoderm 


Ectoderm 


Yolk  entoderm 


Remnant  of 
segmentation  cavity 


FIG.  63. — Transverse  section  of  embryo  of  frog  (Rana  fusca).     Bonnet.     The  section  is  taken  in  front 

of  (anterior  to)  the  blastopore. 

primitive  intestine  (entoderm),  and  that  it  is  within  this  group  of  cells  that  the 
ccelom  finally  appears.  Of  the  yolk  cells,  only  the  outermost  (most  peripheral) 
have  to  do  with  the  formation  of  intestinal  epithelium,  the  remainder  being 
ultimately  used  up  for  the  nutrition  of  the  embryo  (Fig.  65). 

The  formation  of  the  neural  groove  and  neural  tube  from  the  ectoderm  and 
the  separation  of  the  chorda  anlage  from  the  rest  of  the  entoderm  are  much  the 
same  as  in  Triton. 

Mesoderm.  Formation  in  Reptiles  and  Birds. — The  actual  origin  of 
the  mesoderm  in  these  forms  is  very  difficult  to  determine  owing  to  the  pecu- 
liarities of  gastrulation  which  in  turn  are  due  to  the  greatly  increased  amount 
of  yolk.  In  the  lower  forms  it  has  been  seen  that  the  mesoderm  is  primarily  a 
derivative  of  the  entoderm  (Amphioxus,  Fig.  56),  or  of  protentoderm  and  yolk 


GERM   LAYERS. 


79 


entoderm  (frog,  Fig.  53).  One  would  expect,  a  priori,  that  the  mesodermhas 
a  similar  origin  in  the  higher  forms,  even  if  the  entoderm  has  assumed  a  differ- 
ent form  on  account  of  the  fact  that  the  yolk  plays  little  or  no  part  in  the  process 


Neural  Neural 

groove  fold 


Ectoderm 


Mesoderm 


Chorda  anlage 


Entoderm 


FIG.  64. — Transverse    section  through  dorsal  part  of  embryo  of  frog  (Rana  fusca).     Ziegler. 
x,  Groove  indicating  cvagination  to  form  mesoderm. 

of  invagination.  As  a  matter  of  fact,  observations  do  to  a  certain  extent  fulfill 
the  expectation,  but,  on  the  other  hand,  it  is  not  possible  to  trace  the  earliest 
steps  in  its  formation  with  anything  like  the  degree  of  certainty  with  which  it 
can  be  traced  in  the  lower  forms. 


Neural  crest 

Neural  canal 

Primitive  segment 

Notochord 


Coelom  - 


Ventral  mesoderm  < 


Yolk  cells 


|  Ectoderm 

Parietal  mesoderm 
Visceral  mesoderm 


Entoderm 


FIG.  65. — Transverse  section  through  embryo  of  frog  (Rana  fusca).     Bonnet. 


Taking  the  chick  again  as  an  example,  the  mesoderm  appears  first  in  the 

region  of  the  primitive  groove  (blastopore).     Transverse  sections  through  this 

region  show  the  mesoderm  as  several  layers  of  small  irregular  cells  interposed 

laterally  between  the  ectoderm  and  entoderm.     In  the  medial  line,  or  line  of  the 

6 


80 


TEXT-BOOK  OF  EMBRYOLOGY. 


primitive  groove,  all  three  germ  layers  are  blended  into  a  solid  mass  of  cells 
(Fig.  66).  On  the  ground  that  the  primitive  groove  is  the  blastopore,  the  meso- 
derm  here  is  the  peristomal  mesoderm,  the  homologue  of  the  peristomal 
mesoderm  which  encircles  the  blastopore  in  lower  forms  (Fig.  37). 


Primitive  groove  and  folds 


Ectoderm 


Mesoderm 
—  Entoderm 


—  Ectoderm 

—  Mesoderm 

—  Entoderm 


FIG.  66. — Transverse  sections  of  blastoderm  of  chick  (21  hours'  incubation).     Hertwig. 

a,  Section  through  primitive  groove,  posterior  to  Hensen's  node. 

b,  Section  through  Hensen's  node. 

At  a  somewhat  later  stage,  after  the  head  process  appears,  sections  through 
the  head  process  also  show  all  three  germ  layers.  Here  the  ectoderm  is  a  sepa- 
rate layer;  but  the  entoderm  and  mesoderm  are  fused  in  the  medial  line;  that 

Head  process        Neural  plate 


Yolk  cell 


—  Archenteron 


Yolk 


FiG.  67. — Transverse  section  of  blastoderm   of   chick    (21    hours'  incubation).  Hertwig.      Section 
through  head  process,  anterior  to  Hensen's  node. 

is,  in  the  line  of  the  "primitive  intestinal  cord."  Laterally,  the  layers  are  all 
separate,  a  cleft  existing  between  the  mesoderm  and  the  ectoderm  and  another 
between  the  mesoderm  and  the  entoderm  (Fig.  67).  Since  the  mesoderm  in 
the  region  of  the  head  process  is  in  front  of  the  primitive  groove  (blastopore) 


GERM   LAYERS. 


81 


and  appears  in  connection  with  the  "primitive  intestinal  cord,"  it  is  the  gastral 
mesoderm,  the  homologue  of  the  gastral  mesoderm  described  in  lower  forms 
(Fig.  63).  Here  also,  as  in  the  case  of  the  peristomal  mesoderm,  the  mesoderm 
is  primarily  a  solid  plate  of  cells.  Furthermore,  immediately  in  front  of  the 
primitive  groove  the  gastral  mesoderm  is  continuous  with  the  peristomal. 

At  a  still  later  stage  the  gastral  mesoderm  is  found  to  be  separated  from  the 
entoderm,  so  that  the  "primitive  intestinal  cord"  (now  the  notochord)  separates 
the  mesoderm  of  the  two  sides  in  the  medial  line  (Fig.  68). 


Neural  plate 


Notochord 


""  Ectoderm 
—  Mesoderm 
1  Entoderm 
•-"""  Archenteron 


FIG.  68. — Transverse  section  of  blastoderm  of  chick  (40  hours'  incubation).     Hertwig. 
Section  taken  short  distance  anterior  to  Hensen's  node. 

Comparing  the  conditions  in  sections  through  the  head  process  in  the  chick 
with  sections  through  the  body  region  of  the  frog  (Figs.  63  and  64),  a  fairly 
clear  homology  may  be  drawn. 

While  in  the  stages  just  described  in  the  chick  the  mesoderm  is  present  and 
interposed  between  the  ectoderm  and  entoderm,  the  crucial  point  is  its  actual 
origin.  In  the  lower  forms  it  originated  from  the  entoderm,  that  is,  from  the 
cells  which  have  been  invaginated  at  the  blastopore.  In  the  chick  the  blasto- 
pore, which  is  crescent-shaped,  is  transformed  into  a  longitudinal  structure— 


Mesoderm       Primitive  groove 


FIG.  69. — Transverse  section  of  blastoderm  of  chick  (10  hours'  incubation).     Hertwig. 
Section  taken  through  primitive  groove  and  streak. 

the  primitive  groove — but  still  the  blastopore.  As  the  crescentic  blastopore 
becomes  longitudinal,  the  two  horns  come  together  and  fuse  (see  p.  65),  and 
the  line  of  fusion  still  represents  the  area  of  invagination,  where  some  of  the 
surface  cells  have  grown  under  the  remaining  surface  cells  to  form  the  entoderm 
(protentoderm).  And  it  is  along  this  area  of  invagination  that  the  mesoderm 
first  appears.  In  very  early  stages  there  is  an  especially  active  cell  proliferation 
in  the  thickened  layer  of  cells  which  represents  the  primitive  streak.  This 
activity  gives  rise  to  a  mass  of  cells  which  lie  immediately  beneath  the  primitive 


82 


TEXT-BOOK  OF  EMBRYOLOGY. 


groove  and  represent  the  first  mesodermal  cells  (Fig.  69).  It  is  reasonable  to 
assign  the  origin  of  these  cells  to  the  cells  which  have  been  invaginated  along  the 
line  of  the  primitive  groove  (blastopore).  These  invaginated  cells  constitute 
the  protentoderm,  hence  the  mesodermal  cells  may  be  considered  as  derivatives 
of  the  protentoderm. 

As  proliferation  continues,  the  mesodermal  cells  spread  out  between  the 
ectoderm  and  entoderm  (which  is  here  yolk  entoderm)  (Fig.  70).     Finally,  the 


Ectoderm     p.gr. 


Mesoderm 


—  Ectoderm 
Entoderm 


Yolk 


FIG.  70. — Transverse  section  of  blastoderm  of  chick  (slightly  older  than  that  shown  in  Fig.  69). 

Heitung. 
Section  taken  through  primitive  groove  (p.gr.)  and  streak. 

mesoderm  fuses  with  the  yolk  entoderm,  so  that  all  three  germ  layers  are  fused 
beneath  the  primitive  groove  (Fig.  66).  The  fusion  between  the  mesoderm  and 
yolk  entoderm  in  this  region  is  a  secondary  matter. 

That  the  peristomal  mesoderm  is  a  derivative  of  the  invaginated  cells  is 
even  more  clearly  demonstrated  in  Fig.  71,  in  which  the  two  lips  of  the  blasto- 
pore have  not  yet  fused. 


Primitive  fold          Primitive  groove 


FIG.  71. — Transverse  section  through  primitive  streak  and  primitive  groove  of  Diomedea. 

Schauinsland. 

In  front  of  the  primitive  groove,  that  is,  in  the  region  of  the  head  process,  the 
gastral  mesoderm  is  at  first  seen  to  be  continuous  with  the  "primitive  intestinal 
cord"  (Fig.  67);  later  it  becomes  separated  on  each  side  from  the  "primitive 
intestinal  cord"  (now  the  notochord).  While  the  actual  process  has  not  been 
observed,  it  is  reasonable  to  assume  that  the  mesoderm  is  here  also  a  derivative 
of  the  "primitive  intestinal  cord,"  and  since  the  latter  is  produced  by  the  in- 
vagination  (gastrulation,  see  p.  66)  and  consists  of  protentoderm,  the  gastral 


GERM   LAYERS. 


83 


mesoderm  is  a  derivative  of  the  protentoderm  or  invaginated  cells.     Also,  as  the 
invagination  is  a  continuous  process  from  the  first  formation  of  the  crescentic 


Ectoderm 


Neural 

tube 


Entoderm 


Ccelom 


FIG.  72. — Transverse  section  of  chick  embryo  (2  days  incubation).     Photograph. 
The   parietal   mesoderm    (lying   above  the   ccelom)    is  not   labeled.     The  two  large  vessels  under 
the  primitive  segments  are  the  primitive  aortae.     Spaces  separating  germ  layers  are  due  to 
shrinkage. 

groove  up  through  the  formation  of  the  "primitive  intestinal  cord"  (see  p.  66), 
one  can  readily  understand  how  the  mesoderm  is  first  formed  in  the  line  of  the 
primitive  groove  and  continues  to  be  formed  progressively  forward  as  the  invagi- 


Area  pellucida 
Area  vasculosa 


Head  fold 
Xeural  groove 

Primitive  segment 
Primitive  groove 


FIG.  73. — Dorsal  view  of  duck  embryo,  with  two  pairs  of  primitive  segments.     Bonnet. 

nation  pushes  farther  and  farther  forward  to  form  the  "  primitive  intestinal 
cord."  The  gastral  mesoderm  is  thus  from  its  beginning  continuous  with  the 
peristomal  mesoderm,  the  two  together  forming  a  single  plate  of  cells. 


84 


TEXT-BOOK  OF  EMBRYOLOGY. 


As  described  above,  the  mesoderm  of  the  chick  is  at  first  a  solid  plate  of  cells. 
The  cavity  in  the  mesoderm — the  ccelom — appears  as  the  result  of  a  splitting 
of  the  originally  solid  mesoderm  layer  into  two  sublayers — the  parietal  and  the 
visceral  (Fig.  72).  At  the  same  time  that  portion  of  the  mesoderm  which  lies 
adjacent  to  the  neural  groove  on  both  sides  of  the  medial  line  becomes  differen- 
tiated into  two  series  of  bilaterally  symmetrical  segments — the  primitive  seg- 
ments, which  are  connected  with  one  another  by  intermediate  thinner  parts 
(Figs.  73,  74  and  72).  The  splitting  of  the  mesoderm  to  form  the  ccelom  begins 
some  distance  from  the  medial  line  and  progresses  both  laterally  and  medially. 


Neuropore 


Fore-brain  vesicle 


Head  fold 


Area  pellucida 

Area  vasculosa 

Area  opaca 

Yolk 


Edge  of 
blastoderm 


Proamnion 


Mid-  and  hind- 
brain  vesicles 


Neural  fold 


Primitive 
groove 


FIG.  74. — Dorsal  view  of  chick  embryo  with  ten  pairs  of  primitive  segments.     Bonnet. 

The  ccelom  does  not,  however,  reach  the  primitive  segments,  for  a  small  solid 
mass  of  cells — the  intermediate  cell  mass  (Fig.  81) — always  intervenes  between 
the  ccelom  and  the  segments.  Furthermore,  the  ccelom  from  the  beginning 
shows  no  segmentation. 

The  formation  of  the  neural  groove  and  neural  tube  from  the  ectoderm  and 
the  separation  of  the  chorda  anlage  from  the  entoderm  are  much  the  same  as  in 
the  frog.  A  decided  difference  is,  however,  to  be  noted  in  the  shape  of  the 
chick's  blastoderm.  Since  in  this  case  the  yolk  plays  but  a  small  part  in  seg- 
mentation, the  germ  layers  at  first  lie  flat  upon  the  surface  of  the  yolk,  the 


GERM   LAYERS. 


85 


archenteron  being  a  flat  cavity  between  the  entoderm  and  the  yolk  (Figs.  67,  68 
and  69).  The  tubular  form  of  the  intestine  is  brought  about  later  in  connection 
with  the  constriction  of  the  embryo  from  the  yolk  sac  (p.  140;  see  also  forma- 
tion of  primitive  gut,  p.  317). 

Mesoderm  Formation  in  Mammals. — In  Mammals  the  same  difficulties 
are  met  with  in  determining  the  origin  of  the  mesoderm  as  in  the  chick.  At  the 
same  time,  transverse  sections  through  the  developing  mammalian  blastoderm 

Ectoderm 


Mesoderm 


Ba 


Meso- 
derm 


Mesoderm 


Yolk  entoderm  Pr.st 


FIG.  75. — Transverse  sections  of  embryonic  disk  of  dog.     Bonnet. 
Sections  of  disk  shown  in  Fig.  53.     Letters  and  numbers  at  right  (Sj-S4)  indicate  plane  of  sections 
in  Fig.    53.     P.gr.,  Primitive  groove;  Pr.int.co.,   primitive  intestinal  cord;  Pr.st.,  all  three 
germ  layers  fused  in  primitive  streak. 

at  different  stages  show  conditions  which  bear  much  resemblance  to  those  in  the 
chick,  and  lead  toward  the  conclusion  that  the  processes  in  the  two  cases  are 
much  alike. 

Referring  back  to  gastrulation,  it  will  be  remembered  that  on  surface  view 
the  germ  disks  of  the  chick  and  of  the  dog  were  very  similar  (compare  Fig.  46 
with  Fig.  53,  and  Fig.  50  with  Fig.  54,  a).  After  the  formation  of  the  primitive 
streak  in  the  dog,  sections  through  this  region  show  the  mesoderm  interposed 
between  the  ectoderm  and  entoderm  (here  yolk  entoderm)  and  all  three  germ 


86 


TEXT-BOOK  OF  EMBRYOLOGY. 


layers  fused  beneath  the  primitive  groove  (Fig.  75,  S3  and  S4;  compare  with 
Fig.  66).  The  origin  of  the  mesoderm  is  probably,  as  in  the  chick,  to  be  at- 
tributed to  the  invaginated  cells  (protentoderm)  along  the  line  of  the  primitive 
groove.  The  mesodermal  cells  first  appear  as  a  small  mass  beneath  the  primi- 
tive groove  (Fig.  76,  a) ;  they  then  spread  out  laterally  between  the  ectoderm  and 
(yolk)  entoderm  (Fig.  76,  b).  Beneath  the  point  of  origin,  that  is,  along  the 


Primitive  streak    Entoderm      Mesoderm      Ectoderm 


FIG.  76. — Transverse  sections  of  embryonic  disks  of  rabbit,  (a)  Kolliker,  (b)  Rail, 
a,  section  through  primitive  streak  of  embryo  of  6  days  and  18  hours;  b,  section  through  Hensen's 
node  of  embryo  of  7  days  and  3  hours. 

line  of  the  primitive  groove,  they  finally  fuse  with  the  (yolk)  entoderm  (Figs. 
75,  S3  and  S4;  compare  Figs.  76,  a  and  b,  and  Figs.  75,  S3  and  S4  with  Figs.  69, 
70  and  66). 

In  the  region  of  the  head  process,  as  in  the  chick,  sections  show  at  first  the 
entoderm  and  mesoderm  fused  in  the  medial  line,  and  the  ectoderm  as  a  sepa- 
rate layer  (Fig.  77  and  Fig.  75,  S2).  The  entoderm  with  which  the  mesoderm  is 


Ectoderm 


Mesoderm       Notochord 
I       I 


Entoderm 


FIG.  77. — Transverse  section  of  embryonic  disk  of  rabbit,     van  Beneden. 

fused  represents  the  invaginated  cells,  that  is,  the  protentoderm  ("primitive 
intestinal  cord");  and,  as  in  the  chick,  it  seems  reasonable  to  assume  that  the 
mesoderm  is  derived  from  the  "primitive  intestinal  cord"  (protentoderm)  and 
grows  out  laterally  between  the  ectoderm  and  entoderm  (compare  Fig.  75,  S2 
with  Fig.  67). 

A  little  later,  in  the  region  of  the  head  process,  the  mesoderm  on  each  side  is 


GERM  LAYERS. 


87 


found  to  be  separated  from  the  parent  tissue  ("primitive  intestinal  cord"),  and 
the  latter  now  represents  the  anlage  of  the  notochord  (compare  Fig.  72  with 
Fig.  78). 

On  the  ground  that  the  primitive  groove  is  the  blastopore,  the  mesoderm 
arising  in  that  region  is  the  peristomal  mesoderm;  that  arising  from  the 
"primitive  intestinal  cord"  in  front  of  the  primitive  groove  is  the  gastral  meso- 

Mesoderm        Ectoderm        Neural  groove 
i 


408^ 

$%KV*™fc-  **$X-:J*$ 

¥%lj$%^^ 


Yolk  entoderm 


Chordal  plate 


FIG.  78.—  Transverse  section  of  embryonic  disk  of  dog.     Bonnet. 
Section  taken  near  anterior  end  of  head  process. 

derm.  The  peristomal  and  gastral  portion  together  constitute  a  continuous 
plate  of  cells  interposed  between  the  ectoderm  and  entoderm,  which  has  been 
derived  from  the  invaginated  cells  of  the  protentoderm. 

In  a  few  Mammals  (sheep,  roe,  shrew),  mesoderm  has  been  seen  to  arise 
some  distance  from  the  primitive  streak  and  head  process  (Fig.  79).  This  has 
been  called  the  peripheral  mesoderm,  but  it  soon  unites  with  the  peristomal  and 
gastral. 

Embryonic  disk 


Area  of 

invagination 


Nuclei  of 
yolk  entoderm 


Ectoderm 


FIG.  79. — Surface  view  of  embryonic  disk  of  sheep.     Bonnet. 
Disk  is  at  that  stage  of  development  when  gastrulation  begins  (in  region  marked  area  of  invagination). 

Primarily,  the  mesoderm  is  a  solid  plate  of  cells  with  no  indication  of  a  body 
cavity  (ccelom).  A  little  later  the  mesoderm  splits  into  two  layers,  the  parietal 
and  the  visceral,  between  which  lies  the  ccelom  (Fig.  81).  The  splitting  does 
not  effect,  however,  the  mesoderm  which  lies  adjacent  to  the  neural  groove  on 
both  sides  of  the  medial  line,  for  this  portion  becomes  differentiated  into  two 
series  of  bilaterally  symmetrical  segments— the  primitive  segments  (Figs.  80  and 


'88 


TEXT-BOOK  OF  EMBRYOLOGY. 


Prim,  pericard. 
cavity 

Anlage   _ 
of  heart 


Telencephalon 
Diencephalon 
Mesencephalon 

Metencephalon 
Myelencephalon 


Peripheral  limit 
of  coelom 


FIG.  80. — Dorsal  view  of  dog  embryo  with  ten  pairs  of  primitive  segments.     Bonnet. 


Prim.    Intermed 
seg.      cell  mass 


Parietal  and 


esoderm 


derm 


Chordal 
plate 


Coelom         Entoderm        Blood  vessels 
FiG.  81. — Transverse  section  of  dog  embryo  with  ten  pairs  of  primitive  segments.     Bonnet. 


GERM   LAYERS. 


89 


8r).  The  splitting  of  the  mesoderm  begins  some  distance  from  the  medial  line 
and  proceeds  both  laterally  and  medially,  but  does  not  extend  quite  to  the 
primitive  segments.  Thus  a  solid  plate  of  cells  still  remains  between  the  ccelom 
and  the  segments — the  intermediate  cell  mass  (Fig.  81).  The  ccelom  shows  no 
segmentation.  (Compare  Fig.  80  with  Fig.  74  and  Fig.  81  with  Fig.  72.) 

The  formation  of  the  neural  groove  and  tube  from  the  ectoderm  and  the 
separation  of  the  chorda  from  the  entoderm  are  processes  quite  analogous  to  the 
development  of  those  same  structures  in  the  lower  forms. 

As  in  the  chick,  so  also  in  Mammals,  the  blastoderm  is  at  first  spread  out  flat, 
forming  the  roof,  so  to  speak,  of  the  yolk  sac.  At  a  later  period,  in  connection 
with  the  closure  of  the  gut  and  the  establishment  of  the  external  forms  of  the 
body,  the  blastoderm  assumes  a  tubular  shape  (see  p.  140). 

A  comparison  of  the  foregoing  description  of  the  formation  of  the  mesoderm 
in  Mammals  with  the  description  of  the  corresponding  processes  in  the  chick 
(p.  79)  shows  their  essential  similarity. 


Strand  of  mesoderm 
in  exocoelom 


Part  of  exocoelom 

Trophoderm 

Mesoderm  of  chorion 
Ectoderm  of  amnion 
Entoderm 
Amniotic  cavity 
Embryonic  ectoderm 
Mesoderm 
Yolk  cavity 

Mesoderm 


FIG.  82. — Section  through  human  chorion,   amnion,  embryonic  disk,  and  yolk  sac.     Peters. 

Compare  with  Fig.  83. 

The  Germ  Layers  in  Man. 

Of  the  actual  formation  of  the  germ  layers  in  man,  practically  nothing  is 
known.  There  are  no  observations  on  the  segmentation  of  the  ovum,  the  first 
differentiation  of  cells,  or  the  origin  of  the  embryonic  disk  and  germ  layers. 
A  very  young  human  ovum,  described  by  Leopold,  does  not  show  any  structures 
which  can  be  interpreted  as  the  embryonic  disk  or  any  part  of  it.  Another 


90 


TEXT-BOOK  OF  EMBRYOLOGY. 


young  ovum  described  by  Peters  shows  all  three  germ  layers  and  the  flat  embry- 
onic disk.  Bryce  and  Teacher  have  recently  described  an  ovum,  the  youngest 
on  record,  in  which  all  three  germ  layers  are  formed  (see  Fig.  106;  cf.  Fig.  83). 
A  section  through  the  ovum  described  by  Peters  (Fig.  82)  shows  the  ectoderm 
as  a  flat  layer  of  stratified  or  pseudostratified  cells,  the  margin  of  which  is  re- 
flected dorsally  as  the  lining  of  the  roof  of  the  amniotic  cavity  (compare  Fig.  52,^). 
Beneath  the  ectoderm  is  a  layer  of  cells — the  mesoderm — which  is  continu- 


Coagulum 


Trophoderm 


Uterine  epithelium 


Gland 


Decidua  basalis 


Blood 


FIG.  83. — Section  through  very  young  human  chorionic  vesicle  embedded  in  the 

uterine  mucosa.     Peters. 

The  vesicle  measured  2.4  x  1.8  mm.,  the  embryo  .19  mm.  Peters  reckoned  the  age  as  3  or  4  days, 
but  later  studies  of  other  embryos  go  to  show  that  the  age  is  much  greater;  Bryce  and 
Teacher  estimate  it  at  14  to  15  days. 

ous  at  its  margin  with  the  mesoderm  of  the  roof  of  the  amnion,  with  mesoderm 
lining  the  chorionic  vesicle,  and  also  with  the  mesoderm  covering  the  yolk  sac 
Fig.  83).  Beneath  the  mesoderm  of  the  embryonic  disk  is  a  layer  of  entoderm 
which  also  extends  ventrally  to  line  the  yolk  sac.  There  is  here  no  trace  of  an 
invaginated  entoderm  from  which  the  mesoderm  might  arise. 

Graf  Spec  has  described  an  ovum  somewhat  older  than  Peters',  in  which  the 
embryonic  disk  shows  certain  features  which  are  comparable  with  those  in 
lower  Mammals.  On  surface  view  (Fig.  84),  the  primitive  groove  is  especially 


GERM   LAYERS. 


91 


prominent  and  the  opening  at  its  anterior  end,  corresponding  to  Hensen's  node, 
is  usually  well  marked.  The  line  of  the  head  process  is  strongly  marked  by  a 
deep  groove — the  neural  groove  (compare  Fig.  84  with  Fig.  54,  a). 

A  longitudinal  section  in  the  medial  line  of  this  disk  (Fig.  85)  shows  a  re- 
markable similarity  to  a  corresponding  section  of  the  bat's  disk  (Fig.  55).  The 
ectoderm  consists  of  a  single  layer  of  columnar  cells  interrupted  only  at  the 
opening  of  the  blast opore  (anterior  end  of  the  primitive  groove).  The  entoderm 
(chorda  anlage)  also  consists  of  a  single  layer  of  cells  which  is  continuous  at  the 
blastopore  with  the  ectoderm.  In  the  region  of  the  primitive  groove  the  per- 


Yolk  sac 


Amnion 


Neural  groove  — * 


Chorion  — - 


V^     <^f 


FIG.  84. — Dorsal  view  of  human  embryo,  two  millimeters  in  length,  with  yolk  sac. 

von  Spec,  Kollmann. 
The  amnion  is  opened  dorsally. 


istomal  mesoderm  is  present.  The  embryonic  disk  forms  the  roof,  so  to  speak, 
of  the  yolk  sac. 

A  transverse  section  (Fig.  86)  through  the  primitive  groove  shows  all  three 
germ  layers  fused  in  the  medial  line,  but  separated  laterally.  In  this  case  there 
is  a  striking  resemblance  to  the  condition  seen  in  a  corresponding  section  of  the 
rabbit's  disk  (Fig.  87). 

Apart  from  the  embryonic  disk,  the  conditions  are  very  similar  to  those  in 
Peters'  ovum  (compare  Figs.  85  and  82). 

The  unusual  feature  in  both  these  embrvos  is  the  enormous  extent  of  the 


92 


TEXT-BOOK  OF  EMBRYOLOGY. 


mesoderm.     In  Graf  Spec's  ovum  both  longitudinal  and  transverse  sections 
would  suggest  the  same  origin  for  the  intraembryonic  mesoderm  as  in  lower 


Chorionic  villi 


Mesoderm 
of  yolk  sac 


Blood  vessel 


FIG.  85. — Medial  section  of  human  embryo  shown  in  Fig.  84.     -von  Spec,  Kollmann. 

Mammals,  but  the  extent  of  the  extraembryonic  mesoderm,  at  this  early  stage 
of  the  embryonic  disk,  would  indicate  a  departure  from  the  conditions  seen  in 
the  lower  Mammals.  In  other  words,  it  scarcely  seems  possible  that  the 

Ecto- 
Mesoderm   derm    Primitive  groove 


Ectoderrr 


Parietal  mesoderm 
Visceral  mesoderm 

Entoderm 
FIG.  86. — Transverse  section  through  primitive  streak  of  embryo  shown  in  Fig.  84.     von  Spec. 

mesoderm  which  lines  the  chorionic  vesicle  and  covers  the  yolk  sac  has  grown 
out  from  the  mesoderm  which  arises  within  the  embryonic  disk;  it  seems  more 


GERM   LAYERS. 


93 


Parietal  mesoderm 
Visceral  mesoderm 


Primitive  groove 

Primitive  fold 


Entoderm  • 
FIG.  87. — Transverse  section  through  primitive  groove  of  rabbit  embryo,     van  Beneden. 


D 


FIG.  88. — Diagrams  representing  hypothetical  stages  in  the  development  of  the  human  embryo. 

A,  Morula;  compare  with  Fig.  33,  a.  B,  Morula  with  differentiated  superficial  cells;  compare  with 
Fig.  33,  b.  C,  Central  cells  have  become  vacuolized  to  form  the  yolk  cavity,  leaving  a  small 
group  (the  inner  cell  mass)  attached  to  the  enveloping  layer  (trophoderm) ;  compare  with 
Fig.  33,  d.  D,  Cells  of  the  inner  cell  mass  which  are  adjacent  to  the  yolk  cavity  have  become 
differentiated  and  have  begun  to  grow  around  the  cavity,  forming  the  entoderm;  compare 
with  Fig.  52,  a. 


94 


TEXT-BOOK  OF  EMBRYOLOGY. 


reasonable  to  suppose  that  it  has  arisen  outside  the  embryonic  disk  and  united 
with  the  intraembryonic  mesoderm  secondarily. 

While  neither  the  origin  of  the  extraembryonic  mesoderm,  nor  its  behavior 
up  to  the  stage  in  Bryce  and  Teacher's  ovum,  has  been  observed  in  man,  it  is 
possible  to  construct  hypothetical  diagrams  which  allow  of  comparison  with 
what  actually  occurs  in  the  lower  Mammals.  The  morula,  the  differentiation 


Anjr]L<ftic     Cavity 
Ectoctern-j. 
Entoderm 


FIG.  89. — Diagrams  representing  hypothetical  stages  in  the  development  of  the 

human  embryo  (to  follow  Fig.  88). 

A,  Entoderm  surrounds  the  yolk  cavity;  part  of  the  cells  of  the  inner  cell  mass  have  become 
vacuolated,  thus  forming  the  amniotic  cavity,  while  the  remainder  constitute  the  embryonic 
ectoderm;  compare  with  Fig.  52.  B,  Mesoderm  (represented  by  dotted  portion)  has  appeared 
between  the  entoderm  and  trophoderm,  between  the  entoderm  and  ectoderm  of  the  embryonic 
disk,  and  in  the  roof  of  the  amnion.  C,  The  mesoderm  around  the  yolk  cavity  has  split  into 
a  parietal  and  a  visceral  layer,  the  cleft  between  being  the  anlage  of  the  extraembryonic 
body  cavity  (exoccelom). 

of  the  superficial  layer  of  cells,  the  formation  of  the  trophoderm  and  inner  cell 
mass,  and  the  differentiation  of  the  primary  entoderm  may  be  represented 
hypothetically  by  the  diagrams  in  Fig.  88.  These  are  quite  comparable  with 
the  corresponding  stages  of  development  in  the  bat  (Fig.  33).  In  Fig.  89,  A, 
the  amniotic  cavity  formed  by  a  vacuolization  of  a  part  of  the  inner  cell  mass  is 
shown,  and  also  the  entoderm  lining  the  entire  yolk  cavity.  This  is  also  com- 


GERM  LAYERS. 


95 


parable  with  conditions  in  the  bat  (Fig.  52).  In  the  next  stage  (Fig.  89,  B) 
the  mesoderm  is  present  all  the  way  around  between  the  trophoderm  and  ento- 
derm, in  the  roof  of  the  amniotic  cavity,  and  between  the  ectoderm  and  entoderm 
in  the  embryonic  disk.  It  is  possible  that  the  mesoderm  arises  in  situ  as  a  deriv- 
ative of  the  entoderm  or  trophoderm.  Since  in  the  lower  Mammals  it  arises 
from  entoderm,  a  similar  origin  here  seems  the  more  reasonable. 


5taJLk 


aytois 


D 


FIG.  90. — Diagrams  representing  stages  of  development  of  the  human  embryo  (to  follow  Fig.  89). 
A,  A  stage  that  corresponds  approximately  to  those  of  Peters'  and  Bryce-Teacher's  embryos  (Figs. 
83  and  107).  Owing  to  the  rapid  enlargement  of  the  chorionic  vesicle,  the  extraembryonic 
body  cavity  has  become  much  larger  than  in  Fig.  89,  C.  B,  A  stage  (in  longitudinal  section) 
corresponding  to  that  of  von  Spec's  embryo  (Fig.  85).  Only  a  part  of  the  chorion  is  shown; 
the  embryonic  disk  is  slightly  constricted  from  the  yolk  sac;  note  the  belly  stalk,  comparing 
with  A.  C,  Transverse  section,  same  stage  as  B.  D,  Longitudinal  section,  stage  somewhat 
later  than  B.  Note  the  greater  degree  of  constriction  between  the  embryo  and  yolk  sac,  and 
the  larger  amnion. 


In  the  majority  of  the  lower  Mammals  the  intraembryonic  mesoderm  arises 
from  the  entoderm  and  then  grows  out  into  the  wall  of  the  blastodermic  vesicle. 
In  a  few,  however  (sheep,  roe,  shrew),  the  peripheral  mesoderm  (p.  87) 
arises  outside  of  the  embryonic  disk  and  unites  with  the  intraembryonic  meso- 
derm secondarily.  It  might  be  suggested  that  the  formation  of  peripheral 


96  TEXT-BOOK  OF  EMBRYOLOGY. 

mesoderm  outside  of  the  embryonic  disk  is  an  intermediate  step  between  the 
formation  of  mesoderm  entirely  within  the  embryonic  disk  and  its  formation 
around  the  entire  vesicle,  as  in  the  hypothetical  case. 

Neither  in  Peters'  nor  in  Graf  Spec's  ovum  is  any  embryonic  body  cavity 
present.  But  in  both  cases  a  very  large  cavity  exists  between  the  mesoderm  of 
the  yolk  sac  and  that  of  the  chorion.  This  cavity — the  extraembryonic  body 
cavity  (exocodom) — probably  arises  by  a  splitting  of  the  extraembryonic  meso- 
derm into  two  layers,  parietal  and  visceral,  just  as  the  embryonic  body  cavity  in 
other  Mammals  is  the  result  of  a  splitting  of  the  intraembryonic  mesoderm 
(p.  87).  The  splitting  would  occur  as  shown  in  Fig.  89,  C.  The  parietal 
layer  which  with  the  trophoderm  becomes  the  chorion,  then  grows  rapidly  and 
becomes  widely  separated  from  the  visceral  layer,  the  latter  with  the  entoderm 
constituting  the  wall  of  the  yolk  sac.  Thus  a  stage  is  reached  which  is  shown  in 
Fig.  89,  C,  and  which  corresponds  with  Peters'  ovum  (Fig.  83).  The  embry- 
onic disk  with  its  yolk  sac  and  amniotic  cavity  occupies  but  a  small  space  within 
the  chorionic  vesicle.  Consult  also  Fig.  106,  showing  the  Bryce-Teacher  ovum. 

The  stage  corresponding  to  Graf  Spee's  ovum  would  be  produced  by  a  fur- 
ther splitting  of  the  mesoderm  in  the  roof  of  the  amnion,  so  that  finally  the  em- 
bryonic disk  and  yolk  sac  remain  attached  to  the  chorion  only  by  a  band  of 
mesoderm,  the  belly  stalk  (Fig.  90;  compare  with  Fig.  85). 

Even  at  this  stage,  no  body  cavity  is  present  within  the  embryonic  disk 
(Fig.  86).  When  it  does  appear,  however,  it  becomes  continuous  laterally  with 
the  exoccelom  (see  Chap.  XIV),  and  the  parietal  and  visceral  layers  of  meso- 
derm within  the  embryonic  body  are  continuous,  respectively,  with  the  parietal 
and  visceral  extraembryonic  mesoderm. 

PRACTICAL  SUGGESTIONS. 

For  a  complete  demonstration  of  the  formation  of  the  germ  layers,  especially  of  the 
mesoderm,  in  any  class  of  animals,  sections  of  many  successive  stages  are  necessary.  A  few 
specimens,  however,  suffice  to  illustrate  certain  principles  of  development. 

The  formation  of  the  gastrula  in  Invertebrates  is  fairly  well  illustrated  by  the  star-fish. 
After  the  blastulae  appear  (see  "Practical  Suggestions,"  p.  53),  they  may  be  observed  from 
time  to  time  within  the  next  few  hours  and  the  various  steps  in  the  invagination  process 
made  out  quite  definitely.  Any  of  these  stages  may  be  preserved  in  the  same  manner  as  the 
earlier  stages  (p.  53). 

The  formation  of  a  gastrula  from  a  blastula,  in  which  there  is  a  considerable  amount  of 
yolk,  is  seen  in  the  case  of  the  common  frog.  The  ova  are  taken  at  a  time  when  a  small 
crescentic  depression  (the  blastopore)  appears  at  the  marginal  zone,  and  at  intervals  from 
this  time  until  the  yolk  plug  is  seen  projecting  through  the  blastopore.  They  are  fixed  in 
5  per  cent,  formalin,  stained  in  toto  in  borax -carmin  (p.  53),  cut  in  rather  thick  sections  in 
celloidin,  and  mounted  in  xylol-damar.  The  most  instructive  sections  are  those  which  pass 
through  the  blastopore,  in  the  meridional  plane.  For  means  of  removing  the  gelatinous 
capsules  surrounding  the  eggs,  see  page  629. 


GERM   LAYERS.  97 


Transverse  sections  cut  after  the  gastrula  has  begun  to  elongate  to  form  the  embryonic 
body,  prepared  by  the  same  technic  as  above,  will  show  the  mesoderm  at  each  side  of  the 
primitive  gut. 

Surface  views  are  very  instructive  in  cases  of  discoidal  cleavage.  The  primitive  streak 
is  well  shown  in  the  hen's  egg  during  the  second  half  of  the  first  day  of  incubation.  The 
blastoderm  is  removed  from  the  surface  of  the  yolk,  fixed  in  Zenker's  fluid,  stained  in  Mo  in 
borax-carmin  and  mounted  in  toto  in  xylol-damar  (see  Appendix). 

A  blastoderm  of  the  same  stage  (second  half  of  first  day),  fixed  in  Zenker's  fluid  or  in 
Flemming's  fluid,  preferably  the  latter,  cut  in  paraffin  and  stained  with  Heidenhain's  haema- 
toxylin,  will  show  instructive  pictures  of  the  three  germ  layers  before  the  splitting  of  the 
mesoderm;  and  will  also  show  the  fusion  of  all  three  germ  layers  in  the  line  of  the  primitive 
streak. 

Surface  views  of  the  chick  blastoderm,  during  the  second  day  of  incubation,  are  also 
instructive  as  to  general  topography,  showing  the  neural  groove  (or  tube  if  late  in  the  second 
day)  and  its  relation  to  the  primitive  streak,  the  primitive  segments,  the  area  pellucida  and 
the  area  opaca.  The  blastoderm  is  removed  from  the  surface  of  the  yolk,  fixed  in 
Zenker's  fluid,  stained  in  toto  in  borax-carmin,  and  mounted  in  toto  in  xylol-damar  (see 
Appendix). 

Sections  of  a  blastoderm  of  the  same  stage  (second  day)  are  especially  valuable  in  showing 
the  early  conditions  of  the  germ  layers  after  the  primitive  segments  have  appeared  and  the 
mesoderm  has  split  into  two  layers.  The  blastoderm  is  fixed  in  Flemming's  or  Zenker's 
fluid,  cut  transversely  in  paraffin  and  stained  with  Heidenhain's  haematoxylin.  The  ectoderm 
and  neural  groove  (or  tube),  the  mesoderm  (primitive  segments,  parietal  and  visceral  layers 
with  enclosed  ccelom),  and  the  entoderm  and  notochord  are  very  clearly  shown.  The  visceral 
mesoderm  usually  contains  a  number  of  developing  blood  vessels. 

For  methods  of  procuring  mammalian  blastodermic  vesicles  and  preparing  them  for 
study,  see  page  630. 

References  for  Further  Study. 

ASSHETON,  R.:  The  Reinvestigation  into  the  Early  Stages  of  the  Development  of  the 
Rabbit.  Quart.  Jour,  of  Mic.  Sci.,  Vol.  XXXVII,  1894. 

ASSHETON,  R.:  The  Segmentation  of  the  Ovum  of  the  Sheep,  with  Observations  on  the 
Hypothesis  of  a  Hypoblastic  Origin  for  the  Trophoblast.  Quart.  Jour,  of  Mic.  Sci.,  Vol. 
XLI,  1898. 

VAN  BENEDEN,  E.:  Recherches  sur  les  premiers  stades  du  developpement  du  Murin 
(Vespertilio  murinus).  Anal.  Anz.,  Bd.  XVI,  1899. 

BONNET,  R.:  Lehrbuch  der  Entwicklungsgeschichte.     Berlin,  1907. 

BONNET,  R.:  Beitrage  zur  Embryologie  der  Wiederkauer  gewonnen  aus  Schafei.  Arch. 
f.  Anat.  u.  Physiol.,  Anal.  Abth.,  1884,  1889. 

BONNET,  R.:  Beitrage  zur  Embryologie  des  Hundes.  Anat.  Hefte,  Bd.  IX,  1897;  Bd. 
XVI,  1901. 

BRYCE,  T.  H.,and  TEACHER,  J.  H.:  Early  Development  and  Imbedding  of  the  Human 
Ovum.  Glasgow,  1908. 

HARPER,  E.  H.:  The  Fertilization  and  Early  Development  of  the  Pigeon's  Egg.  Am. 
Jour,  of  Anat.t  Vol.  Ill,  1904. 

HATSCHEK,  B.:  Studien  ttber  Entwicklung  des  Amphioxus.  Arbeiten  aus  dem  zool. 
Instit.  zu  Wien,  Bd.  IV,  1881. 


98 


TEXT-BOOK  OF  EMBRYOLOGY. 


HEAPE,  W.:  The  Development  of  the  Mole  (Talpa  europaea).  Quart.  Jour,  of  Mic.  Sci., 
Vol.  XXIII,  1883. 

HERTWIG,  O.:  Die  Lehre  von  den  Keimblattern.  In  Hertwig's  Handbuch  der  vergleich. 
u.  experiment.  Entwickelungslehre  der  Wirbeltiere,  Bd.  I,  Teil  I,  1903. 

HUBRECHT,  A.  A.  W.:  Studies  on  Mammalian  Embryology.  II:  The  Development  of 
the  Germinal  Layers  of  Sorex  vulgaris.  Quart.  Jour,  of  Mic.  Sci.,  Vol.  XXXI,  1890. 

LILLIE,  F.  R.:  The  Development  of  the  Chick.     New  York,  1908. 

McMuRRiCH,  J.  P.:  The  Development  of  the  Human  Body.     Philadelphia,  1907. 

MINOT,  C.  S.:  Laboratory  Text -book  of  Embryology.     Philadelphia,  1903. 

MORGAN,  T.  H.:  The  Development  of  the  Frog's  Egg.     New  York,  1897. 

MORGAN,  T.  H.,  and  HAZEN,  A.  P.:  The  Gastrulation  of  Amphioxus.  Jour,  of  Morphol., 
Vol.  XVI,  1900. 

PATTERSON,  J.  T.:  On  Gastrulation  and  the  Origin  of  the  Primitive  Streak  in  the 
Pigeon's  Egg.  Biolog.  Bull.,  Vol.  XIII,  1907. 

PEEBLES,  F.:  The  Location  of  the  Chick  Embryo  upon  the  Blastoderm.  Jour,  oj  Ex- 
periment. Zool.,  Vol.  I,  1904. 

PETERS,  H.:  Ueber  die  Einbettung  des  menschlichen  Eies  und  das  friiheste  bisher  be- 
kannte  menschliche  Placentationstadium.  Leipzig  u.  Wien,  1899. 

VON  SPEE,  GRAF:  Beobachtungen  an  einer  menschlichen  Keimscheibe  mit  offener  Medul- 
larrinne  und  Canalis  neurentericus,  Arch.  j.  Anal.  u.  Physiol.,  Anat.  Abth.,  1889. 

SOBOTTA,  J. :  Die  Entwickelung  des  Eies  der  Maus  vom  Schluss  der  Furchungsperiode 
bis  zum  Auftreten  der  Amnionfalte.  Arch.  /.  mik.  Anat.,  Bd.  LXI,  1902. 

WILSON,  E.  B.:  Amphioxus  and  the  Mosaic  Theory  of  Development.  Jour,  of  Morphol., 
Vol.  VIII,  1893. 


CHAPTER  VII. 
FCETAL  MEMBRANES. 

In  all  Vertebrates,  with  the  exception  of  Fishes  and  Amphibians  which  lay 
their  eggs  in  water,  there  begin  to  develop  at  a  very  early  stage  certain  accessory 
or  extraembryonic  structures  which  may  be  conveniently  called  jcetal  mem- 
branes. The  development  of  these  structures  is  very  closely  related  to  the  de- 
velopment of  the  embryo  itself,  and  their  presence  is  apparently  largely  depend- 
ent upon  the  very  considerable  length  of  embryonic  life  in  these  forms,  during 
which  it  is  necessary  for  the  embryo  to  maintain  a  definite  relation  to  its  food 
supply  and  to  possess  means  of  discharging  waste  products.  The  fcetal  mem- 
branes, therefore,  have  to  do  with  the  protection  and  nutrition  of  the  growing 
embryo  and  also  are  connected  with  the  care  of  the  waste  products  of  fcetal 
metabolism. 

Under  the  head  of  fcetal  membranes  are  to  be  considered  (i)  the  amnion, 
(2)  the  allantois,  (3)  the  chorion;  also  in  connection  with  these,  the  yolk  sac  and 
the  umbilical  cord. 

The  development  of  these  structures  in  Mammals  and  especially  in  man  is 
extremely  complex  and  can  be  best  understood  by  comparison  with  their  simpler 
development  in  Reptiles  and  Birds. 

FCETAL  MEMBRANES  IN  BIRDS  AND  REPTILES. 

Throughout  these  two  classes  there  is  such  uniformity  in  the  formation  of 
the  fcetal  membranes  that  the  chick  may  be  taken  as  typical.  The  chief 
characteristic  of  these  classes,  as  influencing  the  form  and  structure  of  the  fcetal 
membranes,  is  the  very  large  amount  of  yolk  stored  up  within  the  egg  for  the 
nutrition  of  the  embryo.  This  is  made  necessary  by  the  early  separation  of  the 
egg  from  the  mother,  in  contrast  to  the  close  nutritional  relationship  between 
mother  and  foetus  which  obtains  in  Mammals  (excepting  Monotremes),  where 
the  young  are  retained  within  the  body  of  the  mother  up  to  a  comparatively  late 
developmental  stage. 

The  Amnion. — Returning  to  that  point  in  the  development  of  the  blastoderm 
of  the  chick  where  no  trace  of  amnion  has  as  yet  appeared,  we  recall  that  the 
blastoderm  at  this  stage  consists  of  three  layers,  ectoderm,  mesoderm  and 
entoderm;  that  the  medial  line  of  the  embryo  is  marked  by  the  neural  groove, 
flanked  by  the  neural  folds  which  are  continuous  with  each  other  anteriorly;  that 


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TEXT-BOOK  OF  EMBRYOLOGY. 


on  each  side  of  the  neural  groove  between  ectoderm  and  entoderm  the  mesoderm 
is  a  solid  mass  of  cells,  while  more  laterally  the  mesoderm  is  split,  its  peripheral 
layer  with  the  adjacent  ectoderm  forming  the  somatopleure,  its  central  layer 
with  the  adjacent  entoderm  forming  the  splanchnopleure;  that  between  soma- 
topleure and  splanchnopleure  is  the  body  cavity.  Ventral  to  the  neural  groove 
is  the  notochord,  while  ventral  to  the  latter  is  the  primitive  gut,  the  roof  of  which 
is  formed  of  entoderm  (Fig.  72). 

The  first  indication  of  amnion  formation  is  the  appearance  of  a  fold — the 
head  amniotic  fold — just  in  front  of  the  anterior  union  of  the  neural  folds  (Figs. 


ar.  op.z 


ar.  pel. 


FIG.  91. — Dorsal  view  of  embryo  of  bird  (Phaeton  rubricauda)  with  fifteen  pairs  of 

primitive  segments.     Schauinsland. 

ar.op.1,  Area  opaca,  portion  in  which  mesoderm  is  not  yet  present;  ar.  op.2,  area  opaca;  ar.  pel., 
area  pellucida;  cce.,  bladder-like  dilatation  of  coelom;  cd.  mcs.,  edge  of  mesoderm;  h.am.  /., 
head  amniotic  fold;  pr.  scg.,  primitive  segments;  x,  portion  of  amniotic  fold  containing  no 
mesoderm. 

91  and  97,  &).  This  occurs  during  the  second  day  of  incubation,,  After  the  head 
fold  has  become  well  developed  and  extends  back  over  the  embryo  like  a  hood 
(Fig.  93),  similar  lateral  and  tail  folds  make  their  appearance  (Figs.  92  and  97, 
a  and  £>).  The  folds  continue  to  grow  over  the  dorsum  of  the  embryo  and 
finally  meet  and  fuse  in  the  mid-dorsal  line,  forming  the  amniotic  suture  (Fig.  94). 
The  amniotic  folds  from  the  beginning  involve  the  somatopleure,  that  is, 
the  ectoderm  and  parietal  mesoderm.  But  since  they  arise  some  distance  from 
the  developing  embryonic  body,  the  extraembryonic  portions  only  are  involved. 
At  the  same  time  a  portion  of  the  extraembryonic  body  cavity  is  also  carried 
dorsally  within  the  folds  (Figs  92  and  95),  ."When  the  folds  unite  over  the 


FCETAL  MEMBRANES. 


101 


embryo  they  break  through  at  the  line  of  contact,  thus  leaving  the  outer  layers 
of  the  folds  continuous  and  the  inner  layers  continuous,  with  the  extraembryonic 
body  cavity  continuous  between  the  outer  and  inner  layers. 


n.  tu. 


t.  am.  f. 


ent. 


ent. 


mes.    b.c.  al.    a.m.  e.g. 


FiG.  92 — Medial  section  of  caudal  end  of  chick  embryo  (at  end  of  second 

day  of  incubation).     Duval. 

al.,  Beginning  of  allantoic  evagination;  a.m.,  anal  membrane;  b.c.,  extraembryonic  body  cavity; 
e.g.,  caudal  gut;  ect.,  ectoderm;  ent.,  entoderm;  mes.,  mesoderm;  mes.1,  parietal  mesoderm; 
mes.2,  visceral  mesoderm;  n.tii.,  neural  tube;  pr.g.,  primitive  gut;  t.  am./.,  tail  amniotic 
fold;  ta.,  tail. 

The  result  of  the  development  of  the  amniotic  folds  is: — 
i.  That  the  embryo  is  completely  enclosed  dorsally  and  laterally  by  a  cavity, 
the  amniotic  cavity,  which  is  lined  by  ectoderm  continuous  with  the  ectoderm — 


Area 
opaca 

Edge  of 
mesoderm 


Dorsal  amniotic 
suture 


Primitive 
streak 


FIG.  93.— Dorsal  view  of  embryo  of  albatross,  showing  amnion  covering  cephalic 

end  of  embryo.     Schauinsland. 
^Portion  of  blastoderm  containing  no  mesoderm. 

later  epidermis— of  the  embryo,  the  ectoderm  lining  the  cavity  and  the  overlying 
parietal  mesoderm  together  constituting  the  amnion  (Fig.  96). 

2.  That  the  outer  parts  of  the  amniotic  folds  become  completely  separated 


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TEXT-BOOK  OF  EMBRYOLOGY. 


from  the  inner — the  amnion — to  form  a  second  membrane  consisting  externally 
of  ectoderm,  internally  of  mesoderm  and  called  at  first  the  serosa  or  false 
amnion,  later  the  primitive  chorion  (Fig.  96). 

3.  That  the  extraembryonic  body  cavity  unites  across  the  medial  line 
dorsally,  thus  separating  the  amnion  from  the  primitive  chorion  (Fig.  97,  a,  b 
and  c}. 

During  the  formation  of  the  amnion  the  chick  embryo  is  becoming  more  and 
more  definitely  constricted  off  from  the  underlying  large  yolk  mass  which  is 
liquefying  and  into  which  the  embryo  sinks  somewhat.  At  the  same  time  the 


Ant.  vitelline  vein     Mesoderm 


Omphalomesenteric 
(vitelline)  vein 


Primitive  streak 


Area  opaca 

Sinus  terminalis 

Extraembryonic  body  cavity 

Amnion 
Amniotic  suture 


Area  pellucida 

Amniotic  suture 
/•Lateral  amniotic  fold 

Tail  amniotic  fold 
Area  opaca 


FIG.  94. — Dorsal  view  of  embryo  of  albatross,  showing  amnion  covering  greater 
part  of  embryo.     Schauinsland. 

amniotic  cavity  continues  to  increase  in  size  and  extends  also  ventrally  beneath 
the  embryo  so  that  the  embryo  is  everywhere  enclosed  within  the  amnion 
except  at  its  narrow  connection  with  the  yolk  (Fig.  97,  c,  d). 

The  amniotic  cavity  is  filled  with  fluid,  the  liquor  amnii,  the  origin  of  which 
is  uncertain.  In  it  the  embryo  floats  freely,  attached  only  by  its  ventral  con- 
nection with  the  yolk.  At  about  the  fifth  day  of  incubation  rhythmical  con- 
tractions of  the  amnion  begin.  These  are  apparently  due  to  the  development 
of  contractile  fibers  in  its  mesodermic  tissue  and  give  to  the  embryo  a  regular 
oscillating  motion. 


FCETAL  MEMBRANES. 


103 


The  Yolk  Sac. — The  simplest  type  of  yolk  sac  is  found  in  Amphibians  and 
Fishes.     In  Amphibians  the  yolk  is  enclosed  within  the  embryo,  the  cells  form- 


1.  am.  f.    ex.  b.  c.  ser.        ect. 


pc.  ep.  ht.      pc. 

FIG.  95. — Transverse  section  of  embryo  of  albatross.     Schauinsland. 

Section  taken  through  region  of  heart,  am.,  amnion;  ao.,  aorta;  a.v.v.,  anterior  vitelline  veins; 
ect.,  ectoderm;  ent.,  entoderm;  ep.,  epicardium;  ex.  b.  c.,  extraembryonic  body  cavity;  hi.,  heart; 
l.am.f.,  lateral  amniotic  fold;  pc.,  pericardium;  ph.,  pharynx;  p.  mes.,  parietal  mesoderm; 
ser..  serosa  (chorion);  v.mes.,  visceral  mesoderm;  *  point  at  which  extraembryonic  body 
cavity  passes  over  into  the  intraembryonic  (or  ccclom  proper). 

ing  a  part  of  the  intestinal  wall.     The  superficial  cells  are  split  off  to  form  the 
yolk  ectoderm.     Investing  the  yolk  entoderm  is  the  visceral  mesoderm  which 

ser.  am.  sut.        am. 


—  p.  mes. 


v.  mes. 


ht.      ph.  p.  pc. 

FIG.  96. — Transverse  section  of  embryo  of  albatross.     Schauinsland. 

Section  taken  through  region  of  heart,  am.,  Amnion;  am. sut.,  amniotic  suture;  a.v.v.,  anterior 
vitelline  veins;  ect.,  ectoderm;  ent.,  entoderm;  ex.  b.  c.,  extraembryonic  body  cavity;  ht.,  heart; 
p.  pc.,  primitive  pericardial  cavity;  ph.,  pharynx;  p. mes.,  parietal  mesoderm;  ser.,  serosa 
(chorion);  v. mes.,  visceral  mesoderm;  *  point  at  which  extraembryonic  body  cavity  passes 
over  into  intraembryonic  (or  ccelom). 

is  separated  from  the  parietal  mesoderm  by  the  body  cavity.     Outside  of  the 
parietal  mesoderm  is  the  ectoderm  (Fig.  65).     In  many  of  the  Fishes  the  germ 


104 


TEXT-BOOK  OF  EMBRYOLOGY. 


disk,  as  in  Reptiles  and  Birds,  is  confined  to  one  pole  of  the  egg.  Thus  in  these 
forms  the  embryonic  body  develops  on  the  surface  of  the  large  yolk  mass.  As 
the  embryo  develops  the  germ  layers  simply  grow  around  the  yolk  and  suspend 
it  from  the  ventral  side  of  the  embryo.  At  the  same  time  a  constriction  appears 
between  the  embryo  and  the  yolk  mass,  thus  forming  the  yolk  stalk.  In  this 
case  the  yolk  is  surrounded  from  within  outward,  by  entoderm,  visceral  and 


h.  am.  f. 


t.  am.  f. 
ex.  b.  d. 


FIG.  97. — Diagrams  representing  stages  in  the  development  of  the  foetal  membranes 

in  the  chick.     Hertwig. 

a,  Transverse  section;  b,  c,  d,  longitudinal  sections;  yolk  represented  by  vertical  lines,  al.,  Allantois; 
am.,  amnion;  am.  c.,  amniotic  cavity;  cce.,  ccelom;  dh.,  vitel line  area  between  two  dotted  lines 
which  represent  the  edge  of  the  mesoderm  (at  s.t.)  and  entoderm  (at  z. g.);  dg.,  yolk  stalk; 
ds.,  yolk  sac;  d.umb.,  dermal  umbilicus;  ect.,  ectoderm;  ent.,  entoderm;  ex.b.c.,  extraem- 
bryonic  body  cavity;  gh.,  area  vasculosa;  h.am.}.,  head  amniotic  fold;  m.,  mouth;  p.mes., 
parietal  mesoderm;  s.t.,  sinus  terminalis;  ser.,  serosa  (chorion);  t.am.f.,  tail  amniotic  fold; 
umb.,  umbilicus;  T  mes.,  visceral  mesoderm;  z.  g.,  dotted  line  represents  edge  of  entoderm. 


parietal  mesoderm,  and  ectoderm  (Fig.  98).  The  yolk  furnishes  nutriment  for 
the  embryo.  This  is  conveyed  to  the  tissues  by  means  of  blood  vessels. 
Branches  of  the  vitelline  artery  ramify  in  the  wall  of  the  yolk  sac  (in  the  meso- 
dermal  tissue) ;  the  branches  converge  to  form  the  vitelline  veins  which  carry  the 
blood  back  to  the  embryo. 

In  the  chick,  while  the  amnion  is  forming,  the  inner  germ  layer  gradually 
extends  farther  and  farther  around  the  yolk  (Fig.  97,  a,  b,  c  and  d).     At  the 


FCETAL  MEMBRANES. 


105 


same  time,  as  already  noted  (p.  102),  the  growth  of  the  amnion  ventrally  results 
in  a  sharp  constriction  which  separates  the  embryo  from  the  underlying  yolk. 
This  constriction  is  emphasized  by  constant  lengthwise  growth  of  the  embryo. 
Following  the  gradual  growth  of  the  entoderm  around  the  yolk,  the  mesoderm 
also  gradually  extends  around,  at  the  same  time  splitting  into  visceral  and 
parietal  layers,  so  that  the  entoderm  is  closely  invested  by  visceral  mesoderm 
(Fig.  97,  a,  b,  c  and  d).  Finally,  both  entoderm  and  mesoderm  enclose  com- 
pletely the  mass  of  yolk.  The  yolk  thus  becomes  enclosed  in  the  yolk  sac 
which  consists  of  two  layers,  entoderm  and  visceral  mesoderm.  The  constricted 
connection  between  the  yolk  sac  and  the  embryo  is  the  yolk  stalk.  It  is  seen  by 
reference  to  the  diagrams  (Fig.  97)  that  the  entoderm  lining  the  yolk  sac  i-s 


FIG.  98. — Diagrammatic  longitudinal  section  of  selachian  embryo.     Hertwig. 

a.,  Anus;  d.,  yolk  sac;  dn.,  intestinal  umbilicus;  ds.,  visceral  layer  of  yolk  sac;  hs.,  parietal  layer  of 
yolk  sac;  hn.,  dermal  umbilicus;  III1,  ccelom;  lh2,  exocoelom;  m.,  mouth;  st.,  yolk  stalk. 


directly  continuous  through  the  yolk  stalk  with  the  entoderm  lining  the  primi- 
tive gut.  The  transition  line  between  extra-  and  intraembryonic  entoderm  is 
sometimes  referred  to  as  the  intestinal  umbilicus,  in  contradistinction  to  the  line 
of  union,  on  the  outside  of  the  yolk  stalk,  of  amniotic  and  embryonic  ecto- 
derm (the  latter  becoming  later  the  epidermis)  which  is  known  as  the  dermal 
umbilicus. 

As  in  Fishes  and  Amphibians,  so  also  in  Reptiles  and  Birds,  the  yolk  furnishes 
nourishment  for  the  growing  embryo,  and  is  conveyed  to  the  embryo  by 
the  blood.  At  a  very  early  stage  the  mesoderm  layer  of  the  yolk  sac  (visceral 
mesoderm)  becomes  extremely  vascular.  This  vascular  area  is  indicated  by  an 
irregularly  reticulated  appearance  in  the  periphery  of  the  blastoderm  and  is 
known  as  the  area  vasculosa  (Fig.  74).  The  area  vasculosa  increases  in  size  as 
the  mesoderm  grows  around  the  yolk  and  its  vessels  become  continuous  with 
those  in  the  embryo  (Fig.  212).  Some  of  these  vessels  enlarge  as  branches  of 
two  large  vessels  which  are  given  off  from  the  primitive  aortae,  the  vitelline  or 
omphalomesenteric  arteries.  (When  the  two  aortae  fuse  to  form  a  single 
vessel,  the  proximal  ends  of  the  vitelline  arteries  fuse  likewise.)  The  branches 
of  the  arteries  ramify  in  the  mesoderm  over  the  surface  of  the  yolk  and  then 


•106  TEXT-BOOK  OF  EMBRYOLOGY. 

converge  to  form  other  vessels  which  enter  the  embryo  as  ihemtellineoromphalo- 
mesenteric  veins  (Fig.  213).  As  the  mesoderm  extends  farther  and  farther 
around  the  yolk,  the  vessels  extend  likewise  until  the  entire  yolk  is  surrounded 
by  a  dense  plexus  of  blood  vessels  in  the  wall  of  the  yolk  sac. 

The  Allantois. — While  the  embryonic  intestine  is  first  assuming  the  form 
of  a  tube,  there  grows  out  ventrally  from  near  its  caudal  end,  during  the  third 
day  of  incubation,  a  diverticulum  which  is  the  beginning  of  the  allantois  (Fig. 
99).  This  increases  rapidly  in  size  and  pushes  out  into  the  extraembryonic 
body  cavity  behind  the  yolk  stalk.  As  it  is  a  diverticulum  from  the  intestine, 
it  consists  primarily  of  entoderm.  This  pushes  in  front  of  it,  however,  the 
splanchnic  (visceral)  mesoderm  which  becomes  the  outer  layer  of  the  membrane. 
The  connection  between  the  intestine  and  the  allantois  is  known  as  the  urachus. 
In  the  chick  the  allantois  attains  a  comparatively  large  size,  pushing  out  dorsally 


pr.  seg. 


"~ 


al.  mes.  ent. 


FIG.  99. — Longitudinal  section  of  caudal  end  of  chick  embryo  (end  of  third 

day  of  incubation).     Gasser. 

al.,  Allantois;  al.  p.,  allantois  prominence;  a.m.,  anal  membrane;  am.,  amnion;  am.  c.,  amniotic 
cavity;  e.g.,  caudal  gut;  cce.,  ccelom;  ect.,  ectoderm;  ent.,  entoderm;  ex.  b.  c.,  extraembryonic 
body  cavity;  mes.,  mesoderm;  pr.  g.,  primitive  gut;  t.,  tail. 

between  the  amnion  and  the  primitive  chorion  and  ventrally  between  the  latter 
and  the  yolk  sac  (Fig.  97,  b,  c  and  d).  The  inner  wall  of  the  allantoic  sac  blends 
with  the  amnion  about  the  seventh  day  of  incubation  and  with  the  yolk  sac  con- 
siderably later,  while  the  outer  wall  joins  the  primitive  chorion  to  form  the  true 
chorion,  or  as  it  is  sometimes  designated,  the  attanto-chorion  (see  p.  in).  As 
the  allantois  reaches  the  limit  of  the  yolk,  it  leaves  the  latter,  and  pushing  the 
primitive  chorion  before  it,  continues  around  close  under  the  shell  (Fig.  97) 
until  it  completely  encloses  the  albumen  at  the  small  end  of  the  egg. 
The  allantois  of  the  chick  performs  three  important  functions : 

1.  It  serves  as  a  receptacle  for  the  excretions  of  the  primitive  kidneys. 

2.  United  with  a  part  of  the  primitive  chorion  to  form  the  albumen  sac,  its 
vessels  take  up  the  albumen  as  nourishment  for  the  embryo.     Because  of  this 
function  and  also  because  of  the  fact  that  little  papillae  sometimes  appear  on  the 


FCETAL  MEMBRANES.  107 

inner  surface  of  the  albumen  sac,  evidently  for  the  purpose  of  increasing  its 
absorptive  surface,  this  albumen  sac  has  been  compared  by  some  to  a  placenta. 

3.  It  blends  with  the  primitive  chorion  to  form  the  true  chorion  and  being 
extremely  vascular  and  lying  just  beneath  the  porous  shell,  it  serves  as  the  most 
important  organ  of  fcetal  respiration. 

The  allantois  in  the  chick  is  an  extremely  vascular  organ,  the  network  of 
small  vessels  in  the  wall  being  composed  of  radicals  of  the  allantoic  or  umbilical 
vessels  of  the  embryo.  Soon  after  the  allantois  begins  to  develop,  two 
branches — the  umbilical  arteries — are  given  off  from  the  aorta  near  its  caudal 
end.  These  pass  ventrally  through  the  body  wall  of  the  embryo  and  thence 
out  via  the  umbilicus  to  break  up  into  extensive  networks  of  capillaries  in  the 
mesodermal  layer  of  the  allantois.  The  capillaries  converge  to  form  the  um- 
bilical veins  which  pass  into  the  embryo  via  the  umbilicus  and  thence  cephalad 
to  the  heart. 

During  the  incubation  period  of  the  chick  there  are  two  extraembryonic  sets 
of  blood  vessels.  One  set,  the  vitelline  (omphalomesenteric)  vessels  (p.  238), 
is  concerned  with  carrying  the  yolk  materials  to  the  growing  embryo.  The 
other  set,  the  umbilical  (allantoic)  vessels,  is  chiefly  concerned  with  respiration 
and  carrying  waste  products  to  the  allantois,  but  is  probably  in  part  concerned 
with  conveying  the  albumen  to  the  embryo.  When  the  chick  is  hatched,  and  the 
fcetal  membranes  are  of  no  further  use  and  disappear,  the  extraembryonic  por- 
tions of  the  blood  vessels  also  disappear.  The  intraembryonic  portions  persist, 
in  part,  as  certain  vessels  in  the  adult  organism. 

The  Chorion  or  Serosa. — This  membrane  is  but  little  developed  in  the 
chick  as  compared  with  Mammals,  especially  the  Placentalia.  Its  mode  of 
origin  as  the  outer  leaves  of  the  amniotic  folds,  cut  off  from  the  amnion  by 
dorso-medial  extension  of  the  mesoderm  and  body  cavity,  has  been  described 
(p.  101).  It  consists,  as  there  shown,  of  extraembryonic  ectoderm  and  parietal 
mesoderm  (Fig.  96) .  As  first  formed  it  is  confined  to  the  immediate  region  of 
the  embryo  and  of  the  amnion  to  which  it  is  later  loosely  attached.  It  soon 
extends  ventrally  around  the  yolk  where  it  forms  what  is  sometimes  designated 
the  skin  layer  of  the  yolk  sac.  The  relation  of  the  outer  layers  of  the  allantois 
to  the  chorion  has  been  described  on  page  106,  and  is  illustrated  in  Fig.  99. 

FCETAL  MEMBRANES  IN  MAMMALS. 

The  development  of  the  fcetal  membranes  in  Mammals  presents  no  such 
uniformity  as  is  found  in  Birds  and  Reptiles  where  it  was  possible  to  describe 
their  formation  in  the  chick  as  typical  for  the  two  classes.  In  the  different 
Mammals  much  variation  occurs,  not  only  in  the  first  appearance  of  the  mem- 
branes but  also  in  their  further  development  and  ultimate  structure. 

In  some  forms  (rabbit,  for  example)  the  amnion  develops  in  a  manner  very 


108  TEXT-BOOK  OF  EMBRYOLOGY. 

similar  to  that  in  the  chick;  that  is,  by  a  dorsal  folding  of  the  somatopleure. 
There  is,  however,  no  head  fold  unless  a  temporary  structure  known  as  the 
proamnion  be  considered  as  such.  The  entire  rabbit  amnion  is  formed  by  an 
extension  over  the  embryo  of  the  tail  amniotic  fold.  In  other  forms  (bat  and 
probably  man)  the  amnion  and  amniotic  cavity  arise  in  situ  over  the  embryonic 
disk,  without  any  folding  of  the  somatopleure. 

Yolk  is  almost  entirely  lacking  in  most  Mammals,  but  the  yolk  sac  is  always 
present  although  it  soon  becomes  a  rudimentary  structure.  The  fact  that  the 
yolk  sac  is  always  present  points  toward  the  conclusion  that  Mammals  are 
descended  from  animals  which  possessed  large  ova  with  abundant  yolk.  As  a 
matter  of  fact  the  lowest  Mammals,  the  Monotremes,  possess  large  ova  with 
large  quantities  of  yolk.  These  are  deposited  by  the  female,  are  developed  in  a 
parchment-like  shell,  and  are  carried  about  in  the  brood-pouch. 

The  allantoic  sac  in  many  Mammals  is  a  very  rudimentary  structure  which, 
as  in  the  chick,  always  arises  as  an  evagination  from  the  caudal  end  of  the  gut. 
The  allantoic  blood  vessels,  however,  become  vastly  important  since  they  here 
not  only  carry  off  waste  products  from  the  embryo,  as  in  Reptiles  and  in  Birds, 
but  also  assume  the  function  of  conveying  nutriment  from  the  mother  to  the 
embryo.  In  assuming  this  new  function  they  are  no  longer  concerned  with 
the  allantoic  sac  proper  but  enter  into  a  new  relation  with  the  chorion. 

The  chorion  is  the  most  highly  modified  and  specialized  of  all  the  mam- 
malian fcetal  membranes.  In  some  cases  (the  rabbit,  for  example)  it  arises  in 
connection  with  the  amnion,  as  in  the  chick,  by  a  dorsal  folding  of  the  somato- 
pleure. In  other  cases  (bat  and  probably  man)  it  arises  at  a  very  early  stage, 
partly  as  a  differentiation  of  the  superficial  layer  of  the  morula,  partly  as 
extraembryonic  parietal  mesoderm  which  develops  later.  In  all  cases  where 
the  embryo  is  retained  in  the  uterus  (except  Marsupials)  it  forms  a  most  highly 
specialized  and  complex  structure  which,  in  connection  with  the  allantoic 
vessels,  establishes  the  communication  between  the  mother  and  the  embryo. 

For  the  sake  of  clearness  it  seems  best  to  describe  first  the  earlier  stages  of 
the  fcetal  membranes  in  some  case  where  the  development  resembles  that  of  the 
chick;  then  later  to  consider  the  more  specialized  types  of  development,  the 
ultimate  structure  of  the  membranes,  especially  the  chorion,  and  their  relation 
to  the  embryo  and  the  mother. 

Amnion,  Chorion,  Yolk  Sac,  Allantois,  Umbilical  Cord. — Referring 
back  to  the  mammalian  blastoderm  when  it  consists  of  the  three  germ  layers, 
it  will  be  remembered  that  the  embryonic  disk  forms  the  roof,  so  to  speak,  of  a 
large  cavity — the  yolk  cavity  or  cavity  of  the  blastodermic  vesicle  (Fig.  82) ; 
that  the  ectoderm  of  the  disk  is  continuous  with  a  layer  of  cells  which  extends 
around  the  vesicle — the  extraembryonic  ectoderm;  that  the  entoderm  of  the 
disk  is  continuous  with  the  entoderm  lining  the  cavity  of  the  vesicle;  that  the 


FCETAL  MEMBRANES. 


109 


mesoderm  extends  peripherally  beyond  the  disk  between  the  ectoderm  and 
entoderm  (Fig.  89).  It  will  be  remembered  also  that  the  mesoderm  later  splits 
into  two  layers — the  parietal  and  visceral,  of  which  the  parietal  plus  the  ecto- 
derm forms  the  somatopleure  and  the  visceral  plus  the  entoderm  forms  the 


,L,j,b 


FIG.  ioo. — Diagrams  representing  six  stages  in  the  development  of  the  foetal  membranes 

in  a  mammal.     Modified  from  Kolliker. 

The  ectoderm  is  indicated  by  solid  black  lines;  the  entoderm  by  broken  lines;  the  mesoderm 

by  dotted  lines  and  areas. 

splanchnopleure;  and  that  the  cleft  between  the  two  layers  is  the  body  cavity 
or  crelom. 

In  further  development,  along  with  the  differentiation  of  the  embryonic 
body,  the  somatopleure  begins  to  fold  dorsally  at  a  short  distance  from  the 


110 


TEXT-BOOK  OF  EMBRYOLOGY. 


body  (Fig.  100,  2).  The  folds — amniotic  folds — appear  cranially,  laterally  and 
caudally.  These  folds  continue  to  grow  dorsally  (Fig.  100,  3)  and  finally  meet 
and  fuse  above  the  embryo  (Fig.  100,  4).  They  then  break  through  along  the 
line  of  fusion  so  that  the  extraembryonic  body  cavity  which  has  been  carried  up 
dorsally  over  the  embryo  in  the  amniotic  folds  becomes  continuous  across  the 
mid-dorsal  line.  A  double  membrane  or  rather  two  membranes  are  thus 
formed  which  extend  over  the  embryo.  The  outer  membrane  is  the  chorion 
and  is  composed  from  without  inward  of  ectoderm  and  parietal  mesoderm. 
The  inner  membrane  is  the  amnion  and  is  composed  from  without  inward  of 
parietal  mesoderm  and  ectoderm  (Fig.  100,  5).  Between  the  amnion  and  the 
chorion  is  a  portion  of  the  extraembryonic  body  cavity,  which,  as  already 
mentioned,  was  carried  dorsally  with  the  amniotic  folds  (Fig.  100,  2,  3,  4  and  5). 


Entoderrrr 


Sclerotome       Myotome 


Pronephric 
tubule 


FIG.  101. — Transverse  section  of  a  dog  embryo  with  19  primitive  segments. 
Section  taken  through  sixth  segment. 


Bonnet. 


In  the  manner  just  described  the  amnion  becomes  a  sac  which  at  first  en- 
doses  the  embryo  laterally,  and  then  laterally  and  dorsally  (Fig.  101).  Later 
as  the  embryo  becomes  constricted  off  from  the  underlying  cavity,  the  amnion 
encloses  it  entirely  except  over  a  small  area  on  the  ventral  side  where  the  embryo 
is  attached  to  the  yolk  sac  (Fig.  100,  3,  4  and  5). 

While  the  amnion  is  being  formed,  the  mesoderm  continues  to  extend 
around  the  vesicle  between  the  ectoderm  and  the  entoderm.  At  the  same  time 
it  splits  into  parietal  and  visceral  layers,  of  which  the  parietal  is  applied  to  the 
ectoderm,  and  the  visceral  to  the  entoderm.  In  this  way  the  extraembryonic 
body  cavity  gradually  extends  farther  and  farther  around  the  vesicle  until 
finally  the  somatopleure  is  completely  separated  from  the  splanchnopleure 
(Fig.  100,  3,  4  and  5).  The  extraembryonic  somatopleure  now  forms  a  com- 
plete wall  for  the  vesicle  and  constitutes  the  chorion.  The  extraembryonic 
splanchnopleure  forms  a  complete  wall  for  the  yolk  cavity  and  constitutes  the 
wall  of  the  yolk  sac.  The  proximal  portion  of  the  yolk  sac  becomes  constricted 


FCETAL  MEMBRANES.  HI 

to  form  the  yolk  stalk  which  connects  the  yolk  sac  with  the  ventral  side  of  the 
embryonic  body  (Fig.  100,  5). 

While  the  processes  just  described  have  been  taking  place,  an  evagination  ap- 
pears pushing  out  from  the  ventral  side  of  the  caudal  end  of  the  gut  (Fig.  100, 4). 
This  evagination  grows  out  into  the  extraembryonic  body  cavity  (exo- 
ccelom),  pushing  before  it  the  visceral  layer  of  mesoderm,  thus  giving  rise  to  a 
thin- walled  sac  \vhich  communicates  with  the  gut — the  attantois  (Fig.  100,  5). 
At  this  stage  the  embryonic  body,  with  its  surrounding  amnion  and  appended 
yolk  sac  and  allantois,  lies  within  the  large  vesicle  formed  by  the  chorion.  Up 
to  this  point  the  development  resembles  that  in  the  chick. 

In  succeeding  stages  a  new  connection  is  established  between  the  embryo  and 
the  chorion  in  the  following  manner :  The  amnion  enlarges  and  fills  relatively 
more  of  the  cavity  within  the  chorion,  while  the  yolk  sac  becomes  smaller  and 
the  yolk  stalk  much  attenuated  (Fig.  100,  6).  At  the  same  time  the  allantois 
also  becomes  attenuated  and  its  distal  end  comes  in  contact  with  the  chorion 
(Fig.  100,  6).  The  growth  of  the  amnion  results  in  the  pushing  together  of  the 
attenuated  yolk  stalk  and  allantois  so  that  they  lie  parallel  to  each  other  (Fig. 
100,  6),  and  are  together  invested  by  a  portion  of  the  amnion.  As  already 
described,  both  yolk  stalk  and  allantois  are  composed  of  entoderm  and 
mesoderm  while  the  amnion  is  composed  of  mesoderm  and  ectoderm.  Con- 
sequently when  the  three  structures  come  together  and  fuse,  there  is  formed 
a  mass  of  mesoderm  which  contains  the  entoderm  of  the  yolk  stalk  or  vitelline 
duct  and  the  entoderm  of  the  allantois  or  allantoic  duct,  and  which  is  sur- 
rounded by  the  ectoderm  of  the  amnion.  The  fusion  of  these  three  structures 
in  this  region  thus  produces  a  slender  cord  of  tissue  which  forms  the  union 
between  the  embryo  and  the  chorion  and  which  is  known  as  the  umbilical  cord 
(Fig.  100,  6). 

In  Mammals  the  yolk  sac  contains  little  or  no  yolk  and  consequently  can 
furnish  but  little  nutriment  for  the  embryo;  but  the  union  of  the  allantois  with 
the  chorion,  mentioned  in  the  preceding  paragraph,  allows  the  allantoic  blood 
vessels  to  come  into  connection  with  the  chorion.  And  since  in  Mammals  the 
chorion  is  the  means  of  establishing  the  communication  between  the  embryo 
and  the  mother,  the  allantoic  (umbilical)  vessels  assume  the  function  of  carrying 
nutrient  materials  to  the  embryo  and  also  of  carrying  away  from  the  embryo  its 
waste  products.  (See  p.  242.) 

Further  Development  of  the  Chorion. 

Up  through  the  stages  which  have  been  described  the  correspondence  in  the 

development  of  the  fcetal  membranes  in  Reptiles,  Birds  and  Mammals  is  clear. 

From  now  on,  the  course  of  development  in  Mammals  becomes  more  and 

more  divergent.     The  extensive  development  of  the  yolk  and  yolk  sac  with  its 

8 


112 


TEXT-BOOK  OF  EMBRYOLOGY. 


vascular  system  in  the  egg-laying  Amniotes  has  been  noted.  This  is  dependent 
upon  the  fact  that  the  embryo  very  early  in  its  existence  loses  its  nutritional  con- 
nection with  its  mother  and  is  therefore  dependent  for  its  food  upon  the  yolk 
stored  up  within  the  egg.  This  condition  obtains  up  through  the  lowest  order 
of  Mammals,  the  Monotremes,  which  are  egg-laying  animals.  The  Marsupials 
give  birth  to  young  of  very  immature  development.  In  these  two  orders  of 
Mammals  the  fcetal  membranes  present  essentially  the  same  condition  as  in 
Birds  and  Reptiles.  The  chorion  in  Marsupials,  however,  lies  in  close  ap- 
position to  the  vascular  uterine  mucosa  and  perhaps  provides  for  the  passage  of 


Chorion 


Uterine 
glands 


Blood 
vessels 


Muscularis 


FIG.  102. — Vertical  section  through  wall  of  uterus  and  chorion  of  a  pig.     Photograph. 

Note  especially  the  close  apposition  of  the  chorionic  and  uterine  epithelium  (and  compare  with 

Fig.  103);  note  also  the  enlarged  blood  vessels  in  the  uterine  mucosa. 


nutrition  from  the  mother  to  the  embryo.  In  all  higher  Mammals,  however,  no 
eggs  are  laid  and  the  embryo  early  acquires  an  intimate  nutritional  relation  to 
its  mother.  This  relation  is  maintained  until  the  embryo  has  reached  a  com- 
paratively advanced  stage  of  development.  As  would  be  expected  therefore, 
there  take  place,  coincidently  with  the  change  in  nutritional  relation  between 
mother  and  embryo,  and  dependent  upon  this  changed  relation,  the  already 
noted  decrease  in,  or  entire  loss  of,  yolk  and  at  the  same  time  the  development  of 
a  special  organ  of  relation  between  embryo  and  uterus.  This  organ  is  devel- 
oped mainly  from  the  chorion  which  becomes  highly  specialized  as  compared 
with  the  very  simple  chorion  described  in  the  chick. 


FCETAL  MEMBRANES. 


113 


In  some  Mammals  (e.g.,  pig,  horse,  hippopotamus,  camel)  there  develops  a 
more  intimate  relation  between  the  chorion  and  the  uterine  mucosa.  In  the 
pig,  for  example,  the  chorionic  vesicle  becomes  somewhat  spindle-shaped,  and, 
except  at  its  tapering  ends,  its  surface  is  closely  applied  to  the  surface  of  the 
uterine  mucosa.  On  that  portion  of  the  chorion  which  is  in  contact  with  the 
uterine  mucosa  small  elevations  or  projections  develop  and  fit  into  correspond- 
ing depressions  in  the  mucosa.  These  projections  involve  the  epithelial 
layer  (ectoderm)  of  the  chorion  and  the  adjacent  connective  tissue  (mesoderm) 
(Fig.  102) .  Furthermore,  the  chorionic  epithelial  cells  and  the  uterine  epithelial 


Blood  vessel 
in  chorion 


Chorionic 
epithelium 


Uterine 
epithelium 


Blood  vessel  in 
uterine  mucosa 


FIG.  103. — From  section  through  wall  of  uterus  and  chorion  of  a  pig,  showing  close  relationship 
between  the  epithelium  of  the  uterus  and  that  of  the  chorion.     Photograph. 

cells  acquire  very  intimate  relations  in  that  the  ends  of  the  former  become 
rounded  and  lit  into  depressions  in  the  ends  of  the  latter  (Fig.  103). 

The  allantois  and  allantoic  vessels  in  the  pig  afford  a  good  example  of  the 
transition  from  the  respiratory  and  excretory  functions  which  they  almost  ex- 
clusively possess  in  Reptiles  and  Birds,  to  the  additional  nutritional  function  of 
these  vessels  in  Mammals.  The  allantoic  sac  becomes  large  and  applies  itself 
to  the  inner  surface  of  the  chorion,  so  that  the  blood  vessels  of  the  allantois  also 
grow  into  and  ramify  in  the  mesodermal  layer  of  the  chorion.  This  brings  the 
allantoic  (umbilical)  blood  vessels  containing  the  fcetal  blood  closer  to  the  uterine 
vessels  containing  the  maternal  blood.  The  two  sets  of  vessels  never  come  in 
contact,  however,  being  always  separated  by  the  chorionic  and  uterine  epithe- 


114  TEXT-BOOK  OF  EMBRYOLOGY. 

Hum  and  also  by  some  connective  tissue  of  the  chorion  and  of  the  uterine 
mucosa  (Fig.  103).  Food  materials  for  the  embryo  must,  therefore,  pass  through 
the  connective  tissue  and  the  two  epithelial  layers  in  order  to  get  from  the 
maternal  to  the  fcetal  blood;  and  waste  products  from  the  embryo  must  also  pass 
through  the  same  tissues  to  get  from  the  fcetal  to  the  maternal  blood.  When  the 
fcetal  membranes  of  the  pig  are  expelled  at  birth,  the  rudimentary  chorionic 
villi  simply  withdraw  from  their  sockets  in  the  uterine  mucosa  and  the  chorion 
is  cast  off,  leaving  the  uterine  mucosa  intact. 

In  other  Mammals,  the  attachment  of  the  chorion  to  the  mucous  membrane 
of  the  uterus  is  restricted  to  certain  definite,  highly  specialized  areas.  This 
means  that  the  villi  which  at  first  developed  over  the  entire  chorion,  disappear 
from  the  greater  part  of  it.  Those  villi  which  remain  are  limited  to  a  definite 
area  or  areas  and  develop  extensive  arborizations.  Moreover,  they  do  not 


FIG.  104. — Chorion  of  sheep,  showing  cotyledonary  placenta.     O.  SchuUze. 

simply  fit  into  depressions  in  the  uterine  mucosa,  but  become  much  more 
closely  attached  to  it  while  the  mucosa  increases  in  thickness  and  in  vascularity 
over  the  villous  areas.  There  are  thus  formed  two  distinct  though  intimately 
associated  parts  of  a  structure  which  is  known  as  the  placenta — the  uterine  part 
being  designated  the  maternal  placenta  or  placenta  uterina,  the  fcetal  part  the 
placenta  fcetalis.  Such  Mammals  are  grouped  as  Placentalia.  In  the  sheep 
and  cow  a  number  of  placenta* — multiple  placenta — are  normally  present  (Fig. 
104).  In  the  dog  and  cat  the  placenta  takes  the  shape  of  a  band  or  a  zone 
of  specialized  tissue  encircling  the  germ  vesicle.  This  is  known  as  a  zonular 
placenta.  In  man  a  single  discoidal  area  develops — discoidal  placenta. 

These  different  forms  of  placentae  vary  also  in  regard  to  the  intimacy  with 
which  maternal  and  fcetal  parts  are  associated.  Thus,  for  example,  in  the 
multiple  placentae  of  the  cow  and  sheep,  the  fcetal  placentae  may  be  easily 


FCETAL  MEMBRANES.  115 

pulled  away  from  the  maternal  placentae;  while  in  the  discoidal  placenta  of 
man,  maternal  and  fcetal  parts  are  so  closely  related  that  both  come  away  to- 
gether as  the  after-birth  or  decidua. 

THE  FCETAL  MEMBRANES  IN  MAN. 

The  fcetal  membranes  in  man  are  characterized  by  the  early  development  of 
the  amnion,  the  development  of  an  extremely  complicated  discoidal  placenta  and 
the  rudimentary  condition  of  the  yolk  sac  and  allantois.  The  high  develop- 
ment of  the  placenta — the  organ  of  interchange  between  fcetal  and  maternal 
circulation — is  undoubtedly  dependent  upon  the  very  long  period  of  gestation 
during  which  the  human  foetus  leads  an  entirely  parasitic  existence,  being 
dependent  wholly  upon  the  mother  for  nutrition  and  respiration.  The  exten- 
sive development  of  the  placenta  in  turn  explains  the  rudimentary  condition  of 
the  yolk  sac  and  stalk  and  of  the  allantois,  the  nutritional  and  respiratory  func- 
tions of  these  large  and  important  organs  in  some  of  the  lower  animals,  being  in 
man  taken  up  by  the  placenta. 

The  Amnion. 

In  describing  the  development  of  the  germ  layers  in  the  human  embryo, 
comparisons  were  made  between  one  of  the  youngest  known  human  embryos— 
that  of  Peters — and  the  embryos  of  the  bat  and  mole  (p.  91).  Reference  to  this 
description  and  to  the  figures  shows  that  in  the  bat  and  mole  the  amnion  is 
formed,  not  as  in  the  chick  and  rabbit  by  dorsal  foldings  of  the  somatopleure 
and  fusion  of  these  folds,  but  in  situ  by  a  breaking  down  of  some  of  the  cells  of 
the  inner  cell  mass  and  consequent  cavity  formation.  In  Peters'  embryo  the 
amnion  is  already  present  as  a  closed  cavity.  The  earlier  stages  in  its  forma- 
tion are  not  known.  As  in  the  case  of  the  germ  layers,  however,  the  appear- 
ances in  sections  are  so  closely  similar  as  to  suggest  at  least,  that  the  human 
amnion  is  formed  in  the  same  manner  as  that  of  the  bat  and  mole. 

In  Peters'  ovum  (Fig.  83),  also  in  Bryce-Teacher's  (Fig.  106),  the 
amniotic  cavity  is  seen  already  formed.  It  is  roofed  by  a  single  layer 
of  flat  cells  apparently  analogous  to  the  trophoderm  of  the  bat  (Fig.  52). 
As  in  the  bat  and  chick  this  layer  is  continuous  with  the  higher  ecto- 
derm of  the  embryo  proper  as  represented  here  by  the  embryonic  disk.  The 
extraembryonic  mesoderm  is  already  present  at  this  stage  between  the  ecto- 
derm of  the  amnion  and  the  trophoderm,  the  epithelial  cells  of  the  latter 
being  seen  on  the  surface.  Ventrally  lies  the  yolk  sac  lined  with  entoderm, 
while  laterally  between  the  entoderm  and  ectoderm  is  seen  the  embryonic 
mesoderm.  This  formation  of  the  amnion  in  situ  considerably  shortens  the 
process  of  amnion  formation  as  compared  with  that  in  most  of  the  lower 
animals,  where  it  is  formed  by  dorsal  foldings.  This  results  in  the  very  early 


116  TEXT-BOOK  OF  EMBRYOLOGY. 

formation  of  a  complete  amnion  and  amniotic  cavity  in  such  forms  as  the  bat, 
mole  and  man. 

The  human  amniotic  cavity  is  at  first  small,  the  amnion  covering  only  the 
dorsum  of  the  embryo  to  which  it  is  closely  applied.  The  dorsal  surface  of  the 
disk  is  at  first  concave,  then  flat,  and  later  its  margins  curve  ventrally  as  the  flat 
disk  becomes  transformed  into  the  definite  shape  of  the  embryonic  body.  As 
the  margins  of  the  disk  bend  ventrally  they  carry  with  them  the  attached  amnion. 
As  the  embryo  becomes  constricted  off  from  the  yolk  sac,  the  amnion  is  attached 
only  ventrally  in  the  region  of  the  developing  umbilical  cord.  With  the 
exception  of  this  attachment  the  embryo  thus  comes  to  lie  free,  floating  in 
the  amniotic  fluid  (Fig.  100,  6). 

The  amniotic  cavity,  at  first  small,  increases  rapidly  in  size  and  by  the  third 
month  has  reached  the  limits  of  the  chorionic  vesicle  completely  filling  it.  It 
then  attaches  itself  loosely  to  the  overlying  chorion  thus  completely  obliterating 
the  extraembryonic  body  cavity.  The  amnion  consists  everywhere  of  two 
layers,  an  outer  ectoderm,  the  cells  of  which  are  at  first  flat,  later  cuboidal  or 
even  columnar,  and  an  inner  layer  of  somatic  mesoderm.  At  the  dermal  navel 
(p.  105)  the  amniotic  ectoderm  is  continuous  with  the  surface  ectoderm  (later 
epidermis)  of  the  embryo.  Some  writers  consider  the  fact  that  the  epithelial 
covering  of  the  umbilical  cord  is  stratified  as  indicating  that  it  is  derived  from 
embryonic  ectoderm  rather  than  from  amniotic  ectoderm,  and  describe  the 
transition  between  the  two  as  taking  place  not  at  the  dermal  umbilicus  but  at 
the  attachment  of  the  cord  to  the  placenta.  As  in  lower  forms  (p.  102)  the 
walls  of  the  amniotic  cavity  contain  contractile  elements  which  determine 
rhythmical  contractions  of  the  amnion. 

The  human  amniotic  fluid  is  a  thin,  watery  fluid  of  slightly  alkaline  reaction 
containing  about  one  per  cent,  of  solids,  chiefly  urea,  albumin  and  grape- 
sugar.  The  origin  of  the  fluid  is  not  known.  By  some  it  is  believed  to  be 
mainly  a  secretion  of  the  maternal  tissues,  by  others  as  largely  of  fcetal  origin. 
The  urea  it  contains  is  probably  excreted  by  the  fcetal  kidneys. 

When  the  amount  of  amniotic  fluid  is  excessive  the  condition  is  known  as 
hydramnios.  If,  as  is  sometimes  the  case,  the  amniotic  fluid  is  present  in  very 
small  amount,  adhesions  may  form  between  the  amnion  and  the  embryo. 
These  may  result  in  malformations.  With  or  without  abnormality  in  the 
amount  of  amniotic  fluid,  bands  of  fibrous  tissue  may  stretch  across  the  cavity. 
If  sufficiently  strong  these  may  produce  such  malformations  as  splitting  of 
a  lip  or  of  the  nose,  or  the  partial  or  complete  amputation  of  a  limb. 

In  labor  a  portion  of  the  amnion  filled  with  fluid  usually  precedes  the  head 
through  the  cervical  canal.  It  is  rounded  or  conical,  and  becoming  distended 
and  tense  with  each  uterine  contraction  or  labor  pain,  serves  as  the  natural 
and  most  efficient  dilator  of  the  cervix.  When  the  cervix  is  partially  or  com- 


FOETAL  MEMBRANES.  117 

pletely  dilated,  the  amnion  usually  ruptures — "rupture  of  the  membranes"  — 
and  all  or  a  part  of  the  amniotic  fluid  escapes  as  the  "waters."  Usually  a 
varying  amount  of  the  fluid  remains  behind  the  embryo  being  kept  there  by  the 
head  completely  corking  the  cervix.  This  escapes  with  the  birth  of  the  child. 
In  some  cases  the  amnion  ruptures  at  the  beginning  of  labor,  before  there  has 
been  any  dilatation  of  the  cervix.  The  dilating  must  then  be  done  by  the 
child's  head  or  other  presenting  part.  These  are  much  less  adapted  to  the 
purpose  than  the  bag  of  membranes  and  the  result  is  usually  a  difficult  and 
protracted  "dry"  labor.  Rarely  the  amnion  fails  to  rupture  during  labor  and 
the  child  is  born  within  the  intact  bag  of  membranes.  Such  a  child  is  said  to 
be  born  with  a  "caul." 

The  Yolk  Sac. 

In  the  human  embryo  the  yolk  sac  is  but  a  rudiment  of  the  large  and  im- 
portant organ  found  in  some  of  the  lower  animals.  It  develops  early  and  at  the 
end  of  the  second  week  is  an  almost  spherical  sac  with  a  wide  opening  into  the 
intestine  (Fig.  121),  there  being  but  a  slight  constriction  between  the  embryo 
and  the  yolk  sac.  During  the  third  week  the  yolk  sac  becomes  decidedly  con- 
stricted off  from  the  embryo,  remaining  connected,  however,  with  the  intestine 
by  means  of  a  long  pedicle,  the  yolk  stalk  or  vitelline  duct  (Fig.  123).  As  the 
placenta  is  formed,  and  at  the  same  time  the  umbilical  cord,  the  yolk  sac  becomes 
incorporated  with  the  former,  where  it  may  sometimes  be  found  by  careful 
search  after  birth,  while  the  yolk  stalk  becomes  reduced  to  a  strand  of  cells 
which  traverses  the  entire  length  of  the  umbilical  cord  (p.  134). 

Whatever  function  the  rudimentary  human  yolk  sac  has,  must  be  performed 
early,  as  both  sac  and  stalk  soon  undergo  regressive  changes.  Although  no  true 
yolk  is  present,  the  sac  at  first  contains  fluid  and  its  thick  outer  mesodermal  layer 
is  the  place  of  earliest  blood  and  blood  vessel  formation.  This  would  seem  to 
indicate  that  like  the  larger  yolk  sac  of  lower  animals,  the  human  yolk  sac 
serves  temporarily  as  a  blood-forming  organ. 

In  about  three  per  cent,  of  cases  that  portion  of  the  yolk  stalk  which  lies 
between  the  intestine  and  the  umbilicus  fails  to  degenerate,  retaining  its  lumen 
and  its  connection  with  the  intestine.  It  is  then  known  as  MeckeVs  diverticulum 
and  is  of  considerable  surgical  importance,  as  it  may  become  invaginated  into 
the  small  intestine  and  thus  cause  obstruction  of  the  bowel.  The  blind  end  of 
the  diverticulum  may  remain  attached  to  the  umbilicus,  or  it  may  become  free, 
or  in  rare  cases  the  stalk  may  retain  a  lumen  from  the  intestine  to  the  umbilicus, 
through  which  faeces  may  escape — "faecal  fistula."  Occasionally  a  portion  of 
the  gut  from  which  the  yolk  stalk  is  given  off  extends  for  a  short  distance  into 
the  cord.  If,  as  is  sometimes  the  case,  this  extension  fails  to  retract  before 
birth,  a  congenital  umbilical  hernia  is  the  result  (see  Chap.  XIX). 


118  TEXT-BOOK  OF  EMBRYOLOGY. 

The  Allantois. 

The  human  allantois,  while  analogous  to  the  allantois  of  Birds  and  Reptiles, 
shows  certain  marked  peculiarities  in  its  development,  in  its  relation  to  sur- 
rounding structures  and  in  its  functions. 

Its  development  is  peculiar  in  that  it  does  not  push  out,  as,  for  example,  in 
the  chick,  as  an  evagination  from  the  primitive  gut  into  the  extraembryonic 
body  cavity,  for  at  the  very  early  stage  at  which  the  human  allantois  first  ap- 
pears, the  primitive  gut  is  not  as  yet  constricted  off  from  the  yolk  sac  and  there 
is  no  extraembryonic  body  cavity  into  which  the  allantois  can  extend.  It  will  be 
remembered  that  in  the  formation  of  the  germ  layers  and  in  the  development  of 
the  amnion  the  human  embryo  shows  a  marked  tendency,  as  compared  with 
lower  forms,  toward  a  shortening  of  the  developmental  process.  This  ab- 
breviation and  consequent  very  early  formation  applies  also  to  the  allantois.  As 
the  embryonic  body  assumes  definite  shape  and  the  amnion  is  formed,  there  is 
not  the  complete  separation  of  amnion  from  the  chorion  seen,  for  example,  in  the 
chick,  the  embryo  remaining  connected  posteriorly  with  the  chorion  by  means  of 
a  short  thick  cord  of  mesodermic  tissue.  This  is  known  as  the  belly  stalk.  Into 
this  solid  cord  of  mesodermic  tissue  which  connects  the  embryo  with  the 
chorion,  entodermic  cells  extend.  These  are  derived  from  the  embryonic  en- 
toderm  before  the  constriction  which  differentiates  the  primitive  gut  from  the 
yolk  sac  has  made  its  appearance  (Fig.  85).  According  to  some  there  is  a  true 
evagination  from  the  entodermic  sac  quite  analogous  to  the  evagination  in  the 
chick,  resulting  in  a  long  slender  tube  lined  by  entoderm  and  extending  from 
the  embryo  to  the  chorion.  Others  describe  the  entodermic  outgrowth  as  a 
solid  cord  of  cells.  The  mesodermic  layer  of  the  allantois  is  furnished  by  the 
mesoderm  of  the  belly  stalk.  It  is  to  be  noted  in  this  connection  that  the 
mesoderm  of  the  belly  stalk  is  embryonic  mesoderm  and  that  in  Birds,  for 
example,  this  portion  of  the  mesoderm  splits  into  two  layers,  somatic  and 
splanchnic,  with  the  extraembryonic  body  cavity  between  them.  Into  this 
extraembryonic  body  cavity  the  allantois  extends.  In  man  no  such  splitting 
occurs,  so  that  there  is  no  extraembryonic  body  cavity  into  which  the  allantois 
can  extend.  Instead,  it  grows  out  into  the  belly  stalk. 

The  functions  of  the  human  allantois  are  somewhat  different  from  those  of 
the  allantois  of  the  chick.  In  the  latter  it  is  a  direct  respiratory  organ  in  that  it 
brings  the  embryo  into  relation  with  the  outside  air.  In  man  the  allantois, 
accompanied  by  the  allantoic  (umbilical)  blood  vessels,  comes  into  relation 
with  the  placenta.  As  the  placenta  serves  as  the  medium  of  exchange  between 
fcetal  and  maternal  circulations,  it  acts  as  a  modified  organ  of  respiration.  In 
the  chick  the  allantoic  cavity  also  serves  for  the  reception  of  the  excretions  from 
the  embryo,  the  allantoic  fluid  containing  nitrogenous  excretives.  In  man  all 


FCETAL  MEMBRANES.  119 

such  elimination  is  carried  on  through  the  placenta  and  there  is  consequently 
no  need  for  the  development  of  a  large  allantoic  sac. 

With  development  of  the  placenta,  that  part  of  the  allantoic  stalk  which  lies 
in  the  umbilical  cord  atrophies.  Of  the  embryonic  portion  of  the  allantois, 
or  the  urachus,  on  the  other  hand,  the  proximal  end  communicates  with  the 
urinary  bladder,  while  the  remainder,  which  extends  from  the  bladder  to  the 
umbilicus  becomes  transformed  into  a  fibrous  cord, — the  middle  umbilical 
ligament  (page  404).  Rarely  that  portion  of  the  allantoic  stalk  between  the 
bladder  and  the  umbilicus  remains  patent  and  opening  upon  the  surface 
forms  a  "urinary  fistula,"  allowing  urine  to  escape. 

In  Reptiles  and  Birds  the  omphalomesenteric  vessels,  passing  along  the  yolk 
stalk  and  ramifying  in  the  mesodermal  layer  of  the  yolk  sac,  convey  the  nutrient 
materials  of  the  yolk  to  the  growing  embryo.  Since  the  allantois  is  an  organ  of 
respiration  and  excretion,  the  allantoic  or  umbilical  vessels  have  nothing  to  do 
with  the  actual  nourishment  of  the  embryo  (p.  242).  In  Mammals  the  yolk  sac 
is  of  less  functional  value.  Consequently  the  vitelline  vessels,  although  present 
(Fig.  215),  play  a  less  important  role  in  conveying  nutriment.  The  allantoic 
(umbilical)  vessels,  instead  of  ramifying  in  the  wall  of  the  allantois,  as  in  the 
lower  forms,  come  into  connection  with  the  chorion,  passing  primarily  through 
the  belly  stalk.  Since  the  chorion  becomes  the  organ  of  interchange  between 
the  embryo  and  the  mother,  the  allantoic  vessels  assume  a  new  function,  the 
allantoic  (umbilical)  vein  carrying  food  material  from  the  mother  to  the  em- 
bryo, the  arteries  carrying  waste  products  from  the  embryo  to  the  mother. 
Thus  in  Mammals,  as  the  yolk  sac  and  vitelline  vessels  come  to  play  a  less  im- 
portant role  in  the  nutrition  of  the  embryo,  the  allantoic  vessels,  in  connection 
with  the  chorion,  become  practically  the  only  means  by  which  the  embryo 
receives  its  food-supply. 

The  Chorion  and  the  Decidua. 

When  the  fertilized  ovum  reaches  the  uterus  it  becomes  fixed  or  embedded 
-in  the  uterine  mucosa.  Fixation  usually  occurs  in  the  upper  half  of  the  uterus 
but  may  occur  near  the  cervix.  Rarely  the  ovum  becomes  fixed  to  the  mucous 
membrane  of  the  tube  instead  of  to  that  of  the  uterus,  and,  developing  there, 
gives  rise  to  a  "tubal"  pregnancy — one  of  the  forms  of  extrauterine  gestation. 

Until  recently,  it  was  believed  that  the  ovum  became  attached  to  the  surface 
of  the  mucous  membrane.  Recent  studies  upon  some  of  the  youngest  human 
ova  and  upon  those  of  some  of  the  lower  Mammals,  however,  seem  to  indicate 
that  the  ovum  in  some  way  pushes  itself  into— buries  itself— in  the  uterine 
mucosa  (Fig.  105).  It  is  argued  that  if  the  ovum  simply  attaches  itself  to  the 
surface  of  the  mucosa,  one  would  expect  to  find,  for  a  time  at  least,  epithelium 
between  the  attached  surface  and  the  stroma.  In  a  very  young  human  ovum 


120 


TEXT-BOOK  OF  EMBRYOLOGY. 


no  such  epithelium  was  found  and  the  ovum  had  the  appearance  of  having 
penetrated  the  stroma  by  which  it  was  surrounded  (Fig.  106).  Thus,  for  the 
first  two  weeks  of  gestation,  the  ovum  lies  embedded  in  the  stroma  of  the  uterine 
mucosa,  giving  so  little  surface  indication  of  its  presence  that  it  is  practically 
impossible  to  locate  it  except  by  serial  sections  of  the  entire  mucosa.  After 
two  weeks  the  position  of  the  ovum  begins  to  be  indicated  by  a  slight  prominence 
of  the  mucous  membrane,  the  summit  of  the  prominence  being  marked  by  an 
entrance  plug  consisting  of  coagulum,  cast  off  cells  and  fibrin  (Fig.  83).  In 


Thickening  of 
trophoderm 


Thickening  of 
trophoderm 

Degenerating 
uterine  epithelium 


FIG.  105. — Successive  stages  in  the  implantation  of  the  ovum  of  Spermophilus  cilillus.     Rejsek. 

a.  Ovum  (blastodermic  vesicle)   lying  free  in  the   uterine  cavity,      b,   Later  stage  in  which  the 

syncytial  knob  (thickening  of  trophoderm)  has  penetrated  the  uterine  epithelium  as  far  as 

the  basement  membrane,     c,  Still  later  stage  in  which  the  trophoderm  has  penetrated  the 

uterine  stroma;  the  cells  of  the  uterine  epithelium  at  the  point  of  entrance  are  degenerating. 

the  Bryce-Teacher  ovum  no  such  entrance  plug  was  f0und  (Fig.  106).  At 
this  stage  the  plug  contains  no  glands  or  blood  vessels.  Later  it  becomes 
organized  and  replaced  by  connective  tissue.  Whatever  the  mode  of  fixation 
of  the  ovum  to  the  uterus,  there  immediately  result  important  changes  in  the 
uterine  mucosa  which  lead  to  the  formation  of  the  decidua.  These  changes  are 
both  destructive  and  constructive.  They  are  destructive  in  that  the  epithelial 
covering  of  the  ovum,  the  trophoderm,  has  some  solvent  action  on  the  uterine 
mucosa  and  breaks  down  the  walls  of  the  maternal  blood  vessels  thus  allowing 
the  blood  to  flow  around  the  ovum  (Fig.  106).  They  are  constructive  in  that 
they  result  in  the  formation  of  the  decidua. 


FCETAL  MEMBRANES. 


121 


From  their  relation  to  the  ovum  and  to  the  uterus,  the  deciduse  (by  which  is 
meant  the  uterine  mucosa  of  pregnancy)  have  been  divided  into  the  decidua 
parietalis  or  decidua  vera  the  decidua  basalis  or  serotina,  and  the  decidua  cap- 
sularis  or  refiexa. 


tro. 


cyt.        P.e. 


cap. 


tro.1 


FIG.  106.     Diagram  of  human  ovum  of  13-14  days,  embedded  in  the  uterine 

mucosa.     Bryce  and  Teacher* 

cap.,  Capillary;  cyt.,  cellular  layer  (cyto-trophoderm) ;  cp.,  uterine  epithelium;  gl.,  uterine  gland; 
n.  z.,  necrotic  zone  of  decidua  (uterine  mucosa);  P.e.,  point  of  entrance  of  the  ovum;  try.. 
syncytium  (plasmodium,  plasmodi-trophoderm);  tro.*,  masses  of  vacuolating  syncytium 
invading  capillaries.  The  cavity  of  the  blastodermic  vesicle  is  completely  filled  by  mesoderm, 
and  embedded  therein  are  the  amniotic  and  entodermic  (yolk)  vesicles.  The  natural  pro- 
portions of  the  several  parts  have  been  observed. 


The  decidua  parietalis  is  the  changed  mucosa  of  the  entire  uterus  with  the 
exception  of  that  portion  to  which  the  ovum  is  attached.  The  decidua  basalis 
is  that  portion  of  the  mucosa  to  which  the  ovum  is  attached  and  which  later 
becomes  the  maternal  part  of  the  placenta.  The  decidua  reflexa  is  either  the 

*The  writers  have  been  unfortunate  in  not  having  had  access  to  Bryce  and  Teacher's  splendid 
contribution  (T.  H.  Bryce  and  J.  H.  Teacher:  An  Early  Ovum  Imbedded  in  the  Decidua. 
MacLehose  and  Sons,  Glasgow,  1908)  in  time  to  incorporate  in  the  text  the  result  of  their  investi- 
gation. The  ovum  in  question  was  found  in  a  piece  of  membrane  expelled  during  spontaneous 
abortion  which  occurred  in  a  healthy  young  woman  ten  days  after  the  time  of  the  first  Japsed 
menstrual  flow.  The  age  was  estimated  at  thirteen  to  fourteen  days,  and  the  structure  was  such  as 
to  indicate  an  earlier  stage  than  that  of  Peters',  Jung's,  Merttens',  Leopold's,  or  von  Spec's  embryo, 
thus  making  it  the  youngest  human  ovum  on  record.  The  results  of  the  investigation  are  important 
in  their  bearing  not  only  on  the  implantation  of  the  ovum  in  the  uterine  mucosa  but  also  on  the 
development  of  the  germ  layers. 


122 


TEXT-BOOK  OF  EMBRYOLOGY. 


extension  of  the  mucosa  over  the  ovum  or  that  part  of  the  mucosa  under  which 
the  ovum  buries  itself  (Fig.  107). 

It  will  be  remembered  that  surrounding  the  entire  young  ovum  is  the  chorion 
and  that  this  membrane  consists  of  two  layers,  an  outer  ectoderm  (trophoderm) 
and  an  inner  mesoderm.  In  the  youngest  known  human  embryo  the  chorion  is 


P 


Decidua  parietalis 
Decidua  capsularis 

Decidua  basalis 
Chorion  frondosum 


Placenta 


FIG.  107. — Semidiagramatic  sagittal  section  of  human  uterus  containing  an 

embryo  of  about  five  weeks.     Allen  Thompson. 

a,  Ventral  (anterior)  surface;  c,  cervix  uteri;  ch,  chorian;  g,  outer  limit  of  decidua; 
m,  muscularis;  p,  dorsal  (posterior)  surface. 


a  shaggy  membrane,  its  entire  surface  being  covered  with  small  projections  or 
villi.  Later  these  villi  disappear  from  all  of  the  chorion  except  that  part  of  it 
which  becomes  attached  to  the  uterine  mucosa  and  forms  the  fcetal  part  of  the 
placenta.  The  latter  is  known  as  the  chorion  frondosum,  while  the  smooth 
remainder  of  the  chorion  is  known  as  the  chorion  lave. 
There  are  thus  to  be  considered: 

1.  The  decidua  parietalis. 

2.  The  decidua  capsularis. 

3.  The  decidua  basalis         1 

m,        ,      .       r       j  forming  the  placenta. 

4.  1  he  chorion  trondosum  J 


FCETAL  MEMBRANES.  123 

The  Decidua  Parietalis. — The  changes  in  the  uterine  mucosa  which 
result  in  the  formation  of  the  decidua  parietalis  are  similar  to,  though  more 
extensive  than,  the  changes  which  take  place  during  the  earlier  stages  of  men- 
struation. There  is  congestion  of  the  stroma  with  proliferation  of  the  con- 
nective tissue  elements  and  increase  in  the  length,  breadth  and  tortuosity  of  the 
glands.  These  changes  result  as  in  menstruation  in  thickening  of  the  mucosa 
so  that  at  the  height  of  its  development  the  decidua  parietalis  has  a  thickness  of 
about  i  cm.  It  extends  to  the  internal  os  where  it  ends  abruptly,  there  being  no 
decidua  formed  in  the  cervix. 

In  the  superficial  part  of  the  mucosa  the  glands  wholly  or  almost  wholly 
disappear  and  their  place  is  taken  by  the  proliferating  connective  tissue  of  the 
stroma.  The  result  is  a  layer  of  comparatively  dense  connective  tissue — the 
compact  layer.  Beneath  this  layer  are  found  remains  of  the  uterine  glands  in 
the  shape  of  widely  open,  somewhat  tortuous  spaces  which  extend  for  the  most 
part  parallel  to  the  muscularis.  Some  of  these  glandular  remains  retain  part 
of  their  epithelium.  Lying  in  the  proliferating  stroma,  these  spaces  give  to  this 
layer  the  structure  which  has  led  to  its  being  designated  the  spongy  layer. 

During  the  latter  half  of  pregnancy  the  decidua  parietalis  becomes  greatly 
thinned,  due  apparently  to  pressure  from  the  growing  embryo  with  its  mem- 
branes. With  this  thinning,  the  few  remaining  glands  of  the  compact  layer 
disappear.  The  character  of  the  spongy  layer  changes,  the  glands  collapsing  or 
being  reduced  to  elongated,  narrow  spaces  parallel  to  the  muscularis.  The 
entire  tissue  also  becomes  much  less  vascular  than  in  early  pregnancy. 

If  the  fcetal  membranes  are  in  situ  the  compact  layer  is  in  contact  with  the 
ectodermic  (epithelial)  layer  of  the  chorion.  Ne.xt  to  this  lies  the  mesodermic 
(connective  tissue)  layer  of  the  chorion.  Delicate  adhesions  connect  the 
mesodermic  tissue  of  the  chorion  with  the  mesodermic  layer  of  the  amnion. 
Covering  the  latter  is  the  amniotic  ectoderm  (epithelium). 

The  Decidua  Capsularis. — Early  in  its  development  this  has  essentially 
the  same  structure  as  the  decidua  parietalis.  Its  older  or  more  common  name, 
decidua  reflexa,  indicates  the  earlier  idea  that  this  portion  of  the  decidua  repre- 
sents a  growing  around  or  reflection  of  the  uterine  mucosa  upon  the  attached 
ovum.  Peters,  after  examining  the  very  early  ovum  which  bears  his  name, 
came  to  the  apparently  warranted  conclusion  that  instead  of  the  uterine  mucosa 
growing  out  around  the  ovum,  the  ovum  buries  itself  in  the  mucosa,  and  that  by 
the  time  the  ovum  had  reached  the  size  of  the  one  he  examined  (i  mm.),  it  was 
almost  entirely  covered  over  by  the  mucosa  (Fig.  83).  See  also  Fig.  106.  In 
Peters'  ovum  a  coagulum  consisting  of  blood  cells,  other  cast  off  cells  and 
fibrin  marked  the  point  at  which  the  ovum  probably  entered  the  stroma. 
Later  this  is  replaced  by  connective  tissue  and  for  a  considerable  time  the  point 
is  marked  by  an  area  of  soar  tissue. 


124 


TEXT-BOOK  OF  EMBRYOLOGY. 


By  about  the  fifth  month  the  rapidly  growing  embryo  with  its  membranes 
has  filled  the  uterine  cavity,  and  the  decidua  capsularis,  now  a  very  thin  trans- 
parent membrane,  is  everywhere  pressed  against  the  decidua  parietalis.  It 
ultimately  either  disappears  (Minot)  or  blends  with  the  decidua  parietalis 
(Leopold,  Bonnet). 

The  Decidua  Basalis.— As  the  decidua  basalis  is  that  part  of  the  mucosa 
to  which  the  chorion  frondosum  is  attached,  it  is  convenient  to  consider  the 
two  structures  together. 


Decidua 


"Fastening"  villi 


Terminal  villi 


FIG.  108. — Isolated  villi  from  chorion  frondosum  of  a  human  embryo  of 
eight  weeks.     Kollmann's  Atlas. 

At  a  very  early  stage,  villi  develop  over  the  entire  surface  of  the  chorion 
(Fig.  106).  Very  soon,  however,  the  villi  begin  to  increase  in  number  and  in 
size  over  the  region  of  the  attachment  of  the  ovum  and  to  disappear  from  the 
remainder  of  the  chorion,  thus  leading  to  the  already  mentioned  distinction 
between  the  chorion  frondosum  and  the  chorion  laeve  (p.  122). 

THE  CHORION  FRONDOSUM  or  fcetal  portion  of  the  placenta  consists  of  two 
layers  which  are  not,  however,  sharply  separated. 

1.  The  compact  layer.     This  lies  next  to  the  amnion  and  consists  of  con- 
nective tissue.     At  first  the  latter  is  of  the  more  cellular  embryonal  type.     Later 
it  resembles  adult  fibrous  tissue. 

2.  The  villous  layer.     The  chorionic  villi,  when  they  first  appear,  are  short 


FGETAL  MEMBRANES. 


125 


simple  projections  from  the  epithelial  layer  of  the  chorion  and  consist  wholly  of 
epithelium.  Very  soon,  however,  two  changes  take  place  in  these  projec- 
tions. They  branch  dichotomously  giving  rise  to  secondary  and  tertiary  villi, 
forming  tree-like  structures  (Fig.  108).  At  the  same  time  mesoderm  grows 
into  each  villus  so  that  the  central  part  of  the  originally  solid  epithelial  villus  is 
replaced  by  connective  tissue,  which  thus  forms  a  core  or  axis.  This  connective 
tissue  core  is  at  first  free  from  blood  vessels,  but  toward  the  end  of  the  third  week 
terminals  of  the  umbilical  (allantoic)  vessels  grow  out  into  the  connective  tissue 
and  the  villus  becomes  vascular.  Each  villus  now  consists  of  a  core  of  vascular 
mesodermic  tissue  (embryonal  connective  tissue)  covered  over  by  trophoderm 


Syncytium 


Cellular  layer 
(of  Langhans) 


Blood  vessels 


Mesoderm 
(core  of  villus) 


Intervillous 
space 


FIG.  109. — Section  of  proximal  end  of  villus  from  chorion  frondosum  of  human  embryo 

of  two  months.     Photograph. 

In  the  space  above  the  villus  is  a  mass  of  cells  such  as  are  invariably  found  among  or  attached  to 

the  villi  (see  text,  page  126). 


(epithelium).  At  first  the  epithelium  of  the  villus  consists  of  distinctly  outlined 
cells.  Very  soon,  however,  the  epithelium  shows  a  differentiation  into  two 
layers.  The  inner  layer  lying  next  to  the  mesoderm  is  called  the  layer  of 
Langhans  or  cyto-trophoderm.  Its  cell  boundaries  are  distinct  and  its  nuclei 
frequently  show  mitosis.  The  outer  covering  layer  consists  of  cells  the  bodies 
of  which  have  fused  to  form  a  syncytium — the  syncytial  layer  or  plasmodi- 
trophoderm.  This  is  a  layer  of  densely  stained  protoplasm  of  uneven  thickness 
(Figs.  109  and  no).  It  contains  small  nuclei  which  take  a  dark  stain.  As 
this  layer  is  constantly  growing,  and  as  these  nuclei  do  not  show  mitosis,  it  has 
been  suggested  that  they  probably  multiply  by  direct  division. 


126  TEXT-BOOK  OF  EMBRYOLOGY. 

At  an  early  stage  large  masses  of  cells  appear  among  the  villi,  sometimes  being 
attached  to  the  villi  (Figs.  109  and  in).  The  origin  of  these  masses  is  not  known 
with  certainty.  They  may  represent  thickenings  of  the  syncytium  in  which  the 
cell  boundaries  have  reappeared,  or  they  may  represent  outgrowths  from 
Langhans'  layer.  In  some  cases  the  cells  are  small  with  darkly  staining  nuclei, 
in  other  cases  large  and  homogeneous  with  large  vesicular  nuclei.  Large 
multinuclear  cells,  or  giant  cells,  with  homogeneous  cytoplasm,  also  appear. 
In  some  cases  they  apparently  lie  free  in  the  intervillous  spaces  although 


Hofbauer's  cell 


Capillary 


FIG.  no. — Transverse  section  of  chorion  villus  from  human  embryo  of  two  months,  showing  meso- 
dermal  core  of  villus  and  surrounding  cellular  layer  (cyto-trophoderm)  and  syncytium  (plas- 
modi-trophoderm).  Hofbauer's  cell  is  an  example  of  large  cells  found  in  the  villi,  but  the 
significance  of  which  is  not  known.  From  retouched  photograph.  Grosser. 


it  is  claimed  by  some  investigators  that  they  merely  represent  sections  of 
tips  of  the  syncytial  masses.  A  structure  known  as  canalized  fibrin  (which 
takes  a  brilliant  eosin  stain)  begins  to  develop  in  the  earlier  months  of  preg- 
nancy and  gradually  increases  in  amount  during  the  later  stages.  It  is  found 
in  relation  with  the  large  cell  masses  among  the  villi  and  is  probably  a  degen- 
eration product  of  these  masses. 

In  the  later  months  of  pregnancy  the  covering  layer  of  the  villi  loses  its 
distinctly  epithelial  character,  the  cyto-trophoderm  or  cellular  layer  disappearing 
and  the  plasmodi-trophoderm  or  syncytial  layer  becoming  reduced  to  a  thin 


FOETAL  MEMBRANES. 


127 


homogeneous  membrane.  At  points  in  this  membrane  are  knob-like  projections 
composed  of  darkly  staining  nuclei.  These  are  known  as  nuclear  groups,  or 
proliferation  islands,  and  probably  represent  the  proximal  portions  of  the  large 
cell  masses  already  described  (compare  Figs,  no  and  112). 

Certain  of  the  uterine  stroma  cells  increase  greatly  in  size  and  become  the 
decidual  cells.  These  are  large  cells — 30  to  100  microns — and  vary  in  shape. 
Late  in  pregnancy  they  acquire  a  brownish  color  and  give  this  color  to  the 
superficial  layer  of  the  decidua  parietalis.  Each  cell  usually  contains  a  single 


"Giant"  cell 


Syncytium 


Trophoderm 
mass 


FIG.  in. — Section  of  chorion  of  human  embryo  of  one  month  (9  mm.).     Grosser. 


large  nucleus.  Some  contain  two  or  three  nuclei.  A  few  are  frequently 
multinuclear. 

Some  of  the  chorionic  villi  float  freely  in  the  blood  spaces  of  the  maternal 
placenta — floating  villi;  others  are  attached  to  the  maternal  tissue — fastening 
villi.  The  villi  are  separated  into  larger  and  smaller  groups  or  lobules  by  the 
growth  of  connective  tissue  septa  from  the  maternal  placenta  down  into  the 
decidua  basalis.  These  are  known  as  placental  septa,  while  the  groups  of 
chorionic  villi  are  known  as  cotyledons  (Figs.  113  and  115). 

Both  decidual  cells  and  chorionic  villi  are  important  from  a  diagnostic 


128 


TEXT-BOOK  OF  EMBRYOLOGY. 


standpoint,  as  the  finding  of  them  in  curettings  or  in  a  uterine  discharge  may 
be  accepted  as  proof  of  pregnancy. 

During  the  early  months  of  pregnancy — first  four  months — the  decidua 
basalis  has  essentially  the  same  structure  as  the  decidua  parietalis.  Its  surface 
epithelium  disappears  very  early,  perhaps  even  before  the  attachment  of  the 
ovum.  The  glandular  elements  and  the  connective  tissue  undergo  the  same 
changes  as  in  the  decidua  parietalis  and  here  also  result  in  the  differentiation 
of  a  compact  layer  and  a  spongy  layer.  Both  layers  are  much  thinner  than 
in  the  decidua  parietalis. 

As  already  noted,  connective  tissue  septa  pass  from  the  superficial  layer  of  the 
decidua  basalis  down  into  the  foetal  placenta  subdividing  the  latter  into  cotyle- 
dons. At  the  margin  of  the  placenta  the  decidua  basalis  passes  over  into  the 


Remnant  of  syncytium 
Capillaries  * 

Nuclear  group  •-- 
Artery — 


.Nuclear 
groups 


Remnant 
•  of  syncytium 


3L-  Vein 


'-•'-'A Capillary 

DOS! 

Nuclear  group 
FIG.  112. — Transverse  sections  of  chorionic  villi  at  the  end  of  pregnancy.     Schaper. 

thicker  decidua  parietalis  and  here  the  chorion  is  firmly  attached  to  the  decidua 
basalis. 

There  still  remains  to  be  considered  what  may  be  called  the  border  zone 
between  the  decidua  basalis  and  the  chorion  frondosum.  The  whole  purpose 
of  the  placenta  is  the  interchange  of  materials  between  the  maternal  and  foetal 
circulation.  It  is  in  the  border  zone  that  this  interchange  takes  place.  The 
entire  structure  of  this  zone  is  for  this  function,  while  all  the  rest  of  the  placenta 
serves  to  transport  the  blood  to  and  from  this  area.  We  have  considered  on  the 
maternal  side  the  structure  of  the  superficial  (compact)  layer  of  the  decidua 
basalis  (p.  123),  on  the  fcetal  side  the  structures  of  the  villous  layer  of  the  chorion 
frondosum  (p.  124).  Unfortunately,  this  border  zone  has  an  extremely  com- 
plicated structure  which  is  difficult  of  interpretation  in  the  usual  microscopic 
section.  This  has  led  to  much  confusion  in  description  and  many  differences 
of  opinion  as  to  actual  structure.  We  can  here  consider  only  the  more  generally 


FCETAL  MEMBRANES. 


129 


accepted  facts,  referring  the  student  to  special  articles  on  the  subject  for  further 
details. 

In  the  fully  developed  placenta,  the  chorionic  villi  lie  either  free  (floating 


65 


villi)  or  attached  to  the  decidua  (fastening  villi)  in  what  are  known  as  inter- 
villous  spaces  (Fig.  113).     In  sections  the  villi  are,  on  account  of  their  structure, 


130 


,     TEXT-BOOK  OF  EMBRYOLOGY. 


Blood  vessel 


.>..  .        .  Q 

**%&•'*'&» ••£?*&  **.*•*  e>: .  -\*.^f,-^ 

«*."£•••  Tf??Sf°f?:  .«.«  ^/~Zz,~  ~>.-^r&:''& 


Base  of  villus 


Villi  in  section 


'J''&     ^Uterine  glards 
Base  of  decidua 


^Muscular  coat 
of  uterus 


FIG.  114. — Vertical  section  through  wall  of  uterus  and  placenta  in  situ;  about  seven  months' 

development.     Minot. 


FCETAL  MEMBRANES. 


131 


cut  in  all  directions,  many  sections  of  villi  being  entirely  free  from  their  basal 
connections.  The  villi  thus  present  the  appearance  of  projections,  peninsulas, 
or  islands  lying  in  spaces  filled  with  blood  (Fig.  114). 

Branches  from  the  arteries  of  the  uterine  muscularis  enter  the  decidua  basa- 
lis.  They  take  very  tortuous  courses  through  the  latter  and  in  it  lose  their  con- 
nective tissue  and  muscular  coats,  and,  while  of  considerably  larger  diameter 
than  most  capillaries,  become  reduced  to  endothelial  tubes.  These  follow  the 
intervillous  (placental)  septa  in  which  they  branch  and  from  which  they  finally 
open  directly  into  the  intervillous  spaces  along  the  edges  of  the  cotyledons. 
The  maternal  blood  is  thus  poured  into  the  intervillous  spaces  at  their  peri- 
phery. After  flowing  through  them  it  passes  into  veins  which  leave  the 
intervillous  spaces  near  the  center  of  the  cotyledons  (Fig.  113). 


Chorion  laeve     _ 
Decidua  parietalis' 


Decidua  basalis 


Cotyledon 
(lobe) 


Cotyledon 
(lobe) 


FIG.  115. — Placenta  at  birth,  seen  from  the  uterine  side.     Bonnet. 

The  relation  of  these  spaces  to  the  maternal  blood  vessels  is  not  easy  to  make 
out  in  ordinary  sections,  but  many  observations  have  established  the  fact  that 
both  arteries  and  veins  open  directly  into  the  spaces.  The  entire  system  of 
intervillous  spaces  may  thus  be  considered  as  a  part  of,  or  an  appendage  to,  the 
maternal  vascular  system,  the  maternal  blood  flowing  from  the  arteries  into 
these  spaces  and  returning  from  these  spaces  to  the  mother  through  the  veins. 
The  fcetal  blood,  on  the  other  hand,  circulates  in  the  capillaries  of  the  connective 
tissue  of  the  villi  separated  from  the  maternal  blood  of  the  intervillous  spaces  by 
the  epithelial  villous  covering  already  described  (p.  125).  It  is  between  the 
maternal  blood  of  the  intervillous  spaces  and  the  fcetal  blood  in  the  villous 
capillaries  that  the  interchange  of  material  takes  place.  Both  the  maternal 
and  fcetal  vascular  systems  are  closed  systems  so  that  no  blood  can  pass  directly 


\ 
132  \  TEXT-BOOK  OF  EMBRYOLOGY. 

from  mother  to  foetus  or  from  foetus  to  mother.  This  can  be  absolutely  proved  in 
early  pregnancy  by  the  fact  that  nucleated  red  cells  are  at  this  stage  constantly 
present  in  the  blood  of  the  foetus  but  never  normally  present  in  the  maternal 
circulation.  The  normal  circulation  of  blood  through  spaces  unlined  by  endo- 
thelium  is  such  a  remarkable  exception  in  histology  that  repeated  attempts 
have  been  made  to  demonstrate  an  endothelial  lining  to  the  intervillous  spaces 
but,  up  to  the  present  time,  no  such  lining  has  been  found. 

The  manner  in  which  the  intervillous  spaces  are  formed  still  remains  the 
subject  of  much  controversy.  The  similarity  of  development  in  the  human 
ovum  and  in  the  ovum  of  the  bat  has  already  been  noted.  In  the  bat  the 
chorion  when  first  formed  consists  of  two  thin  layers,  an  inner  mesodermal 
layer  and  an  outer  ectodermal  layer  (trophoderm).  From  analogy  there  is 
every  reason  to  believe  that  the  early  human  chorion  has  the  same  struc- 
ture. Proof  of  this  is,  however,  as  yet  wanting,  as  in  the  earliest  human  ova 
the  trophoderm  is  already  a  thick  layer.  There  are  also  present  over  the 
entire  surface  of  the  chorion  and  thus  in  contact  not  only  with  the  future 
decidua  basalis  but  also  in  contact  with  the  entire  future  decidua  capsularis, 
well  developed  villi,  each  consisting  of  a  core  of  mesoderm  and  of  a  thick  covering 
of  trophoderm  (Fig.  83).  Between  the  villi,  bounded  by  the  villi  and  by  the 
decidua,  are  pools  of  maternal  blood.  Peters  suggested  that  rapid  prolifera- 
tion of  the  cells  of  the  trophoderm  might  result  in  an  opening  up  of  the  maternal 
vessels  with  which  they  came  in  contact  and  give  rise  to  repeated  effusions  of 
maternal  blood.  This  blood  would  be  poured  out  mainly  within  the  tropho- 
derm but  bounded  externally  by  the  decidua.  The  blood  pools  thus  formed 
would  represent  the  first  stage  in  the  formation  of  the  intervillous  spaces.  Ac- 
cording to  Bonnet  and  others  the  chorionic  villi  of  the  developing  placenta  are 
constantly  opening  up  new  decidual  vessels,  the  trophoderm  eroding  or  dis- 
solving more  and  more  decidual  tissue,  so  that  the  intervillous  spaces  are  con- 
stantly increasing  in  size  with  growth  of  the  placenta. 

The  placenta  at  birth  is  a  discoid  mass  of  tissue  between  15  and  20  cm.  in 
diameter,  about  3  to  4  cm.  thick  and  weighs  from  500  to  1200  grms.  As  its 
area  of  attachment  marks  the  point  where  the  ovum  becomes  fixed  to  the 
uterine  mucosa  and  as  the  point  of  fixation  of  the  ovum  varies,  the  placenta  may 
be  attached  to  any  portion  of  the  uterine  wall.  It  is  most  frequently  attached 
in  the  region  of  the  fundus  and  more  frequently  to  the  posterior  wall  than  to 
the  anterior.  If  the  fixation  of  the  ovum  is  sufficiently  loW,  the  placenta  may 
partly  or  completely  close  the  internal  os,  thus  giving  rise  to  what  is  known  as 
placenta  pr&via. 

The  Umbilical  Cord. — As  the  amnion  grows  and  extends  ventrally  with 
the  ventral  bending  of  the  embryonic  disk,  the  yolk  stalk  and  sac,  now  very 
much  attenuated,  become  pressed  against  the  cord  of  mesodermal  tissue  which 


FCETAL  MEMBRANES. 


133 


connects  the  embryo  with  the  chorion,  and  incorporated  with  it  to  form  the 
umbilical  cord  (Figs.  89  and  90). 

The  umbilical  cord  thus  consists  of:  (Fig.  116) : 

1.  Amnion.     This  is  attached  to  the  embryo  at  the  navel.     It  is  at  first 
loosely  connected  with  the  underlying  tissue  of  the  cord  so  that  it  is  easily 
peeled  off;  later  it  becomes  firmly  adherent.     The  epithelium  of  the  amniotic 
covering  of  the  cord  is  stratified  and  is  described  by  some  (Minot,  McMurrich) 
as  of  embryonic  ectodermic  origin  instead  of  as  part  of  the  amnion. 

2.  What  may  be  called  the  ground  substance  or  substantia  propria  of  the 
cord.     This  is  an  embryonic  connective  tissue  often  described  as  "mucous 


Umbilical  vein 


Amnion 


Umbilical 
arteries 


FIG.  116. — Transverse  section  of  umbilical  cord  of  a  pig  embryo  six  inches  in  length.     Photograph. 

tissue."  It  consists  of  a  soft  gelatinous  intercellular  substance  and  irregular, 
branching  stellate  cells.  On  account  of  its  consistency  it  has  been  called 
"Wharton's  jelly." 

3.  Three  umbilical  vessels — two  arteries  and  one  vein.  All  these  vessels 
are  thick  walled  and  the  developing  smooth  muscle  is  in  bundles  separated  by 
considerable  connective  tissue.  The  two  umbilical  arteries  carry  venous  blood 
from  the  foetus  to  the  placenta  where  their  branches  ultimately  give  rise  to  the 
capillaries  of  the  chorionic  villi.  From  the  villi  the  blood  enters  the  terminals 
of  the  umbilical  vein  and  returns  as  arterial  blood  to  the  foetus  (Fig.  217). 

As  they  traverse  the  cord  the  arteries  make  a  number  of  spiral  turns  around 
the  vein  and  give  to  the  cord  the  appearance  of  being  spirally  twisted.  The 


134  \  TEXT-BOOK  OF  EMBRYOLOGY. 

\ 

cause  of  this  twisting  is  not  known.  In  places  where  the  turns  are  quite  abrupt 
and  there  are  considerable  accumulations  of  connective  tissue,  the  cord  has  a 
knotted  appearance.  These  points  are  known  as  false  knots.  Rarely  the  cord 
is  actually  tied  into  a  more  or  less  complex  knot — true  knot — probably  due  to 
movements  of  the  foetus. 

4.  Remnants  of  the  allantoic  stalk  and  of  the  yolk  stalk.  These,  if  present, 
are  continuous  or  broken  cords  of  epithelial  cells.  Rarely  one  or  the  other  may 
retain  its  lumen  or  some  of  the  yolk  stalk  vessels  may  remain. 

As  the  yolk  stalk  is  carried  around  to  be  incorporated  as  part  of  the  umbilical 
cord  there  is  enclosed  with  it  a  small  part  of  the  extraembryonic  body  cavity. 

The  human  umbilical  cord  averages  50  cm.  in  length  and  has  a  diameter  of 
about  1.5  cm. 

The  Expulsion  of  the  Placenta  and  Membranes. — After  the  birth  of  the 
child,  the  uterine  contractions  usually  cease  temporarily  and  the  uterine  walls 
remain  contracted  around  the  placenta.  In  the  course  of  a  few  moments  the 
uterine  contractions  are  resumed  and  the  placenta  and  membranes  are  ex- 
pelled as  the  after -birth. 

The  line  of  separation  of  the  placenta  and  of  the  decidua  parietalis  from  the 
uterine  mucosa  is  through  the  deeper  part  of  the  spongy  layer  (Fig.  113).  By 
this  separation  many  blood  vessels  are  opened,  the  hemorrhage  being  con- 
trolled by  the  firm  contractions  of  the  uterine  muscle.  The  condition  of  the 
uterine  mucosa,  after  child-birth,  has  been  described  as  an  exaggeration  of  its 
condition  at  the  end  of  menstruation.  Reconstruction  of  the  mucosa  takes 
place  by  proliferation  of  the  still  remaining  connective  tissue  and  of  the  gland- 
ular elements. 

Anomalies. 

The  manner  in  which  the  placenta  is  formed — by  excessive  development  of 
the  decidua  and  chorion  over  a  limited  area  and  atrophy  of  the  chorion  through- 
out the  remainder  of  its  extent — suggests  the  most  frequent  variations  from  the 
normal. 

The  villi  instead  of  developing  over  the  usual  discoid al  area  may  develop  along 
a  band-like  area  which  more  or  less  completely  encircles  the  chorion.  This  gives 
rise  to  an  annular  placenta  similar  to  that  seen  in  the  Carnivora.  Continued 
development  of  the  villi  over  the  entire  chorion  may  occur.  This  results  in  a 
thin  "placenta  membranacea."  Such  a  placenta  is  apt  to  be  adherent  and  may 
thus  cause  a  serious  postpartum  condition.  Failure  of  the  villi  to  atrophy  and 
their  continued  development  over  more  than  a  single  area  give  rise  to  variations 
in  form  and  number  of  placentae.  When  there  are  two  not  very  distinctly 
separated  areas  the  condition  is  known  as  placenta  bipartite.  Two  completely 
separated  placentae  with  distinct  branchings  of  the  umbilical  vessels  to  supply 


FCETAL  MEMBRANES.  135 

them  are  known  as  placenta  duplex.  Placenta  triplex  and  up  to  placenta  septu- 
plex  have  been  described.  When  one  or  more  placental  lobules  develop  at  a 
little  distance  from  the  main  placental  mass  but  connected  with  the  latter  by 
blood  vessels,  the  result  is  the  not  uncommon  placenta  succenturiata.  Placenta 
spuria  is  applied  to  such  an  accessory  lobule  when  it  has  no  vascular  connection 
with  the  main  placenta  and  consequently  no  function. 

Anomalies  of  the  placenta  associated  with  multiple  pregnancies  and  with 
anomalies  of  the  foetus  will  be  found  under  their  respective  heads. 

Anomalies  of  the  cord  are  for  the  most  part  dependent  upon  anomalies  of 
the  foetus  and  of  the  placenta. 

PRACTICAL  SUGGESTIONS. 

The  early  formation  of  the  foetal  membranes  can  be  studied  most  conveniently  in  chick 
embryos  of  the  second  and  third  days  of  incubation.  At  the  beginning  of  the  second  day  the 
amniotic  jolds  are  beginning  to  develop  and  show  very  clearly.  Further  development  can  be 
followed  in  successive  stages  up  to  the  end  of  the  third  day,  when  the  amnion  and  chorion 
form  complete  sacs  (Figs.  94  and  96). 

Remove  the  embryo  from  the  egg,  fix  in  Zenker's  or  Perenyi's  fluid,  section  tranversely  in 
paraffin,  and  stain  with  Weigert's  haimatoxylin  and  eosin.  Much  time  can  be  saved  by 
staining  in  Mo  with  borax-carmin  (see  Appendix). 

After  the  amnion  and  chorion  have  grown  dorsally  they  can  be  seen,  if  the  egg  is  opened 
carefully,  as  a  thin  semi-transparent  veil  over  the  embryo,  and  sometimes  the  dorsal  line  of 
fusion  can  be  made  out.  (See  Fig.  94.) 

In  transverse  sections  of  embryos  of  the  second  day  the  anlage  of  the  allantois  can  be 
seen  as  a  ventral  evagination  from  the  caudal  end  of  the  gut.  (See  Fig.  99.) 

The  later  stages  of  the  membranes  in  the  chick  can  be  studied  macroscopically  after 
carefully  turning  the  contents  of  the  egg  into  a  dish  of  warm  salt  solution. 

The  lack  of  knowledge  concerning  the  early  formation  of  the  fcetal  membranes  in  Mammals, 
especially  in  man,  is  due  chiefly  to  the  difficulty  in  procuring  embryos  in  early  stages.  In 
later  stages  the  membranes  can  be  clearly  seen  and  their  relations  ascertained  when  the 
uterus  is  opened.  A  careful  dissection  of  the  uterus  and  membranes  of  some  Mammal 
(the  dog,  for  example)  is  very  instructive.  Occasionally  human  embryos  are  obtained  in 
which  the  membranes  can  be  studied.  (See  Figs.  117  and  118.) 

For  the  study  of  the  relation  between  the  chorion  and  uterus,  the  gravid  uterus  of  the 
pig  furnishes  excellent  material.  The  relation  is  very  simple,  yet  gives  a  clue  to  the  much 
more  complicated  conditions  in  higher  forms.  Fix  pieces  of  the  uterine  wall  with  the  chorion 
in  situ  in  Zenker's  fluid,  cut  sections  vertical  to  the  surface,  and  stain  with  Weigert's  hasma- 
toxylin  and  eosin.  (See  Fig.  102.) 

In  man  the  relations  between  the  chorion  (placenta)  and  uterus  are  extremely  complicated 
and  it  is  difficult  even  to  interpret  the  structures  seen  in  section.  Up  to  the  end  of  the  third 
month,  in  cases  of  spontaneous  abortion,  the  membranes  usually  come  away  intact  with  the 
villi  projecting  from  the  chorion.  For  study  of  the  histological  structure  of  the  chorion  by 
itself,  cut  pieces  from  the  wall  of  the  vesicle,  fix  in  Orth's  fluid,  cut  sections  vertical  to  the 
inner  surface,  and  stain  with  haematoxylin  and  eosin  (see  Appendix).  The  villi  of  course  are 
cut  at  various  angles,  but  their  structure  shows  very  clearly.  (See  Fig.  109.)  Similar  technic 
can  be  used  for  study  of  later  stages  of  the  chorion  frondosum  or  foetal  placenta.  In  the 


136  TEXT-BOOK  OF  EMBRYOLOGY. 

rare  cases  in  which  a  placenta  is  obtained  in  situ,  cut  thin  slices  vertically  through  the  uterine 
wall  and  placenta.  Treat  as  in  the  preceding  technic.  These  sections  are  especially 
valuable  in  showing  the  relations  between  the  maternal  and  foetal  tissues. 

References  for  Further  Study. 

BEJIEKE:  Sehr  junges  menschliches  Ei.  Monatsschr.  j.  Geburtshilje  u.  Gynakologie,  Bd. 
XXII,  1904. 

BONNET,  R.:  Lehrbuch  der  Entwickelungsgeschichte  des  Menschen.     Berlin,  1907. 

BRYCE,  T.  H.:  Embryology.     In  Quain's  Anatomy,  nth  ed.,  Vol.  I,  1908. 

BRYCE,  T.  H.,  and  TEACHER,  ].  H.:  An  Earlv  Ovum  Imbedded  in  the  Decidua. 
Glasgow,  1908. 

FRASSI,  L.:  Ueber  ein  junges  menschliches  Ei  in  situ.  Arch.  }.  mik.  Anat.,  Bd.  LXX, 
1907. 

GROSSER,  O.:  Die  Eihaute  und  der  Placenta.     1908. 

HERTWIG,  O.:  Lehrbuch  der  Entwickelungsgeschichte  des  Menschen  und  der  Wirbel- 
tiere.  Berlin,  1906. 

HOFBAUER,  J.:  Biologic  der  menschlichen  Placenta.     Wien  and  Leipzig,  1905. 

HUBRECHT,  A.  A.  W.:  Placentation  of  Erinaceus  Europaeus.  Quart,  Jour,  of  Mic.  Sri., 
Vol.  XXX,  1889. 

VON  HUEKELOM,  S.:  Ueber  die  menschliche  Placentation.  Archiv.  jilr  Anat.  und Physiol., 
Anat.  Abth.,  1898. 

KEIBEL,  F.,  and  MALL,  F.  P..:  Manual  of  Human  Embryology.     Vol.  I,  1910. 

KOLLMANN,  J.:  Lehrbuch  der  Entwickelungsgeschichte  des  Menschen.     Jena,  1898. 

KOLLMANN,  J.:  Handatlas  der  Entwickelungsgeschichte  des  Menschen.     Bd.  I,  1907. 

LEOPOLD,  G.:  Ueber  ein  sehr  junges  menschliches  Ei  in  situ.     Leipzig,  1906. 

MARCHAND,  F.:  Beobachtungen  an  jungen  menschlichen  Eiern.  Anat.  Hejte,  Bd.  XXL 
1903. 

McMuRRiCH,  J.  P.:  The  Development  of  the  Human  Body.     Philadelphia,  1907. 

MINOT,  C.  S.:  Uterus  and  Embryo.    Jour,  of  Morphcl.,  Vol.  II,  1889. 

MINOT,  C.  S.:  Laboratory  Text -book  of  Embryology.     Philadelphia,  1903. 

PETERS,  H.:  Ueber  die  Einbettung  des  menschlichen  Eies  und  das  fruheste  bisher 
bekannte  menschliche  Placentationsstadium.  Leipzig,  1899. 

MERTTENS,  J.:  Beitrage  zur  normalen  und  pathologischen  Anatomic  der  menschlichen 
Placenta.  Zeitschr.  /.  Geburtshilje  u.  Gynakologie,  Bd.  XXX,  XXXI,  1894. 

REJSEK,  J.:  Anheftung  (Implantation)  des  Saugetiereies  an  die  Uteruswand,  insbesondere 
des  Eies  von  Spermophilus  citillus.  Arch.  j.  mik.  Anat.,  Bd.  LXIII,  1904. 

Rossi  DORIA,  T.:  Ueber  die  Einbettung  des  menschlichen  Eies,  studirt  an  einem  kleinen 
Eie  der  zweiten  Woche.  Arch.  /.  Gyndk.,  Bd.  LXXVI,  1905. 

SELENKA,  E.:  Studien  iiber  die  Entwickelungsgeschichte  der  Tiere;  (Menschenaffen) . 
Wiesbaden,  1901-1906.  Parts  8-10. 

STRAHL,  H. :  Die  Embryonalhiillen  der  Sauger  und  die  Placenta.  In  Hertwig's  Handbuch 
der  vergleich.  u.  experiment.  Entwickelungslehre  der  Wirbeltiere.  Bd.  I,  Teil  II,  1902. 

WEBSTER,  J.  C.:  Human  Placentation.     Chicago,  1901. 


CHAPTER  VIII. 
THE  DEVELOPMENT  OF  THE  EXTERNAL  FORM  OF  THE  BODY. 

The  segmentation  of  the  ovum  and  the  formation  of  the  blastodermic  vesicle 
have  not  been  observed  in  man.  For  these  stages  it  is  necessary,  therefore,  to 
depend  upon  the  lower  Mammals.  In  those  Mammals  in  which  the  processes 
have  been  observed,  the  segmentation  of  the  ovum  produces  a  solid  mass  of 
cells  known  as  the  morula  (Fig.  88;  compare  with  Fig.  33).  The  superficial 
cells  of  the  morula  then  become  differentiated  from  those  in  the  interior.  The 
result  is  a  solid  sphere  composed  of  a  central  mass  of  polyhedral  cells  and  an 
enveloping  layer  of  somewhat  flattened  cells  (Fig.  88;  compare  with  Fig.  33). 
The  cells  of  the  enveloping  layer  become  still  more  differentiated  from  those  of 
the  central  mass,  and  the  sphere  continues  to  increase  in  size  owing  to  the  pro- 
liferation of  both  kinds  of  cells.  The  next  step  in  development  is  the  formation 
of  a  cavity  within  the  sphere.  Among  Invertebrates,  where  but  little  yolk  is 
present  and  where  no  distinct  differentiation  of  the  superficial  cells  occurs,  the 
central  cells  are  displaced,  or  pushed  toward  the  periphery,  so  that  the  morula  is 
changed  into  a  hollow  sphere — the  Uastula — the  wall  of  which  is  composed  of  a 
single  layer  of  cells  (p.  50).  Among  Mammals,  however,  instead  of  a  displace- 
ment of  the  central  cells,  there  appear  within  the  cells  vacuoles  which  continue 
to  enlarge  and  finally  become  confluent,  thus  forming  a  cavity  which  occupies 
the  greater  part  of  the  interior  of  the  sphere.  There  remain  then,  after  the 
vacuolization,  the  enveloping  cells,  or  trophoderm,  and  a  few  of  the  central  cells 
which  are  attached  to  the  trophoderm  over  a  small  area  and  constitute  the 
inner  cell  mass  (Fig.  88).  The  latter  is  the  anlage  of  the  embryonic  body. 
As  stated  on  page  52,  the  cavity  of  the  sphere  in  Mammals  is  not  homologous 
with  the  cavity  of  the  blastula  in  the  lower  forms,  but  the  vacuolization  of  the 
cells  probably  represents  a  belated  and  abortive  attempt  at  yolk  formation. 

Following  the  formation  of  the  yolk  cavity,  those  cells  of  the  inner  cell  mass 
which  border  it  become  differentiated,  proliferate  and  gradually  spread  out  in  a 
single  layer  that  finally  forms  a  complete  lining  for  the  cavity.  The  cells  of  this 
layer  constitute  the  primitive  entoderm  (Fig.  88).  In  the  meantime  some  of  the 
cells  of  the  inner  cell  mass  which  lie  between  the  differentiating  entoderm  and 
the  trophoderm  undergo  a  process  of  vacuolization,  leaving  only  a  single  layer 
closely  applied  to  the  entoderm.  This  layer  is  the  embryonic  ectoderm,  and  the 
newly  formed  cavity  between  it  and  the  trophoderm  is  the  amniotic  cavity 

137 


138  TEXT-BOOK  OF  EMBRYOLOGY. 

(Fig.  89;  compare  with  Fig.  52).     The  further  development  of  the  latter  has 
been  described  on  page  116. 

At  this  stage  the  sphere  contains  two  cavities,  the  larger  yolk  cavity  and  the 
smaller  amniotic  cavity,  separated  by  a  double  layer  of  cells,  the  ectoderm  and 
entoderm,  which  constitute  the  embryonic  disk.  The  greater  part  of  the  wall  of 
the  sphere  is  composed  of  two  layers;  the  portion  forming  the  wall  of  the  larger 
yolk  cavity  being  composed  of  trophoderm  and  entoderm,  the  portion  forming 
the  wall  of  the  smaller  amniotic  cavity  being  composed  of  trophoderm  alone 
(Fig.  89).  The  entire  structure  is  spoken  of  as  the  blastodermic  vesicle. 


FIG.  117. — Human  embryo  of  two  months  (twenty-six  millimeters).     Photograph. 
The  embryo  lies  within  the  chorion  (open  on  one  side),  to  which  it  is  attached  at  the  right  of  the 
figure  by  the  umbilical  cord;  around  the  point  of  attachment  the  chorionic  villi  can  be  seen. 
The  amnion  has  been  opened  and  turned  back. 

The  formation  of  the  mesoderm  has  been  discussed  elsewhere  (Chap.  VI, 
p.  85).  At  this  point  it  is  sufficient  to  say  that  it  appears  in  the  wall  of  the 
yolk  cavity  as  a  third  layer  between  the  trophoderm  and  entoderm,  and,  in  the 
embryonic  disk,  between  the  ectoderm  and  entoderm.  Thus  the  blastodermic 
vesicle  possesses  all  three  germ  layers  (Fig.  89). 

In  the  further  course  of  development  the  mesoderm  splits  into  two  layers, 
an  outer  or  parietal  and  an  inner  or  visceral.  Between  the  layers  a  cleft  ap- 
pears, which  is  completely  bounded  by  mesoderm,  on  the  outer  side  by  the 
parietal,  on  the  inner  side  by  the  visceral.  The  parietal  and  visceral  layers 
are  in  apposition  to  the  trophoderm  and  entoderm  respectively.  The  two 
layers  of  mesoderm  soon  become  widely  separated  owing  to  rapid  growth  of 
the  parietal  layer  and  the  trophoderm.  The  parietal  layer  of  mesoderm  and 


DEVELOPMENT  OF  THE  EXTERNAL  FORM  OF  THE  BODY. 


139 


the  trophoderm  together  constitute  the  chorion;  the  original  cavity  of  the 
blastodermic  vesicle  with  its  wall  of  entoderm  and  visceral  mesoderm  is  the 
yolk  sac;  the  newly  acquired  cavity  between  the  chorion  and  yolk  sac  is  the 
extraembryonic  body  cavity  or  exoccelojn.  The  embryonic  disk  lies  on  one  side 
of,  and  might  be  said  to  form  the  roof  of  the  yolk  cavity. 

A  very  young  human  embryo  described  by  Peters  (Fig.  83)  corresponds  ap- 
proximately to  the  stage  of  development  shown  in  Fig.  90,  A.     The  entire 

Amniotic  cavity 


Muscular  coat 
of  uterus 


Chorionic 

villi  — ; 
Umbilical  — 
cord 


Cervix 


FIG.  118. — Opened  uterus  containing  membranes  and  foetus  of  three  months, 
foetus,  thirty-five  millimeters.     Natural  size.     Bonnet. 


Length  of 


vesicle  measures  about  i  mm.  in  diameter  and  encloses  the  small,  flat  em- 
bryonic disk  with  its  appended  yolk  sac.  The  disk  proper  consists  of  three 
layers  of  cells — the  ectoderm,  mesoderm  and  entoderm.  The  chorion  is  widely 
separated  from  the  yolk  sac  by  the  exocoelom.  See  also  Fig.  106. 

An  embryo  slightly  more  advanced  than  that  described  by  Peters  has  been 
described  by  von  Spee  (Fig.  84).  In  this  case  a  furrow — the  neural  groove — 
appears  on  the  dorsal  (ectodermal)  side  of  the  embryonic  disk,  and  the  latter  is 


140 


TEXT-BOOK  OF  EMBRYOLOGY. 


somewhat  elongated  in  the  direction  of  the  furrow.  At  the  sides  and  ends  the 
disk  is  bent  ventrally  so  that  a  depression  is  formed  around  it.  The  margin  of 
the  disk  is  continuous  with  the  amnion  and  with  the  yolk  sac  (Figs.  85  and  90, 
B,  C).  The  disk  as  a  whole  shows  a  trace  of  constriction  from  the  yolk  sac, 
but  at  one  end  remains  attached  to  the  chorion  by  means  of  a  mesodermal 
structure — the  belly  stalk  (Fig.  85). 

Still  a  little  further  advanced  than  von  Spec's  embryo,  is  one  described  'by 


Cerebral  plate 


Heart 


Ant.  entrance  to 
prim,  gut  (Ant. 
Intest.  portal) 


Neural  tube 


Post,  entrance  to 
prim,  gut  (Post, 
intest.  portalj 


Neural  fold 
Neural  groove 


FIG.  119. — (a)  Ventral  view;  (b)  dorsal  view  of  hu'.-ian  embryo  with  8  pairs  of  primitive 

segments  (2.11  mm.).     Eternod.     From  models  by  Ziegler. 

In  b  the  amnion  has  been  removed,  merely  the  cut  edge  showing;  in  a  the  yolk  sac  has 

been  removed. 

Eternod  (Fig.  119).  What  was  originally  the  embryonic  disk  has  here  become 
more  elongated,  and  has  assumed  a  sort  of  cylindrical  shape  owing  to  the  rolling 
under  of  the  lateral  margins.  As  a  part  of  the  rolling  under  process,  the  depres- 
sion which  originally  surrounded  the  disk  has  become  deeper  and  has  effected  a 
still  greater  degree  of  constriction  between  the  cylindrical  body  and  the  yolk 
sac.  The  caudal  end  of  the  body  remains  attached  to  the  chorion  by  means  of 
the  belly  stalk.  The  lips  of  the  neural  groove  have  turned  dorsally  and  fused  in 
the  middorsal  line  along  part  of  their  course. 


DEVELOPMENT  OF  THE  EXTERNAL  FORM  OF  THE  BODY. 


141 


From  a  comparison  of  the  three  stages  which  have  been  mentioned,  it  can  be 
inferred  that  the  process  which  establishes  the  cylindrical  form  of  the  body  is 
essentially  one  of  bending  of  the  margins  of  the  embryonic  disk  with  accom- 
panying elongation  of  the  disk.  It  is  obvious  that  the  process  begins  at  an  early 
period — coincident  with  the  appearance  of  the  primitive  streak  and  neural 
groove.  The  margins  of  the  disk  bend  ventrally  and  form  the  lateral  body  walls 
(Figs.  90,  C,  and  84) ,  then  bend  inward  and  finally  meet  in  the  midventral  line 
to  form  the  ventral  body  wall.  At  the  same  time  the  body  gradually  be- 
comes elongated  in  the  direction  of  the  neural  groove  (Fig.  119).  When  the 
body  walls  bend  inward  a  constriction  is  produced  between  the  body  and  the 


Fore-brain 


O  m  phalomesenteric 
vein 


Yolk  sac 


Amnion 


t-    Belly  stalk 


FIG.  120. — Dorso-lateral  view  of  human  embryo  with  fourteen  pairs  of  primitive 
segments  (2.5  mm.).     Kollmann. 


yolk  sac.  As  the  body  and  yolk  sac  enlarge,  the  constriction  becomes  relatively 
deeper  until  the  yolk  sac  is  attached  to  the  ventral  side  of  the  body  by  a  slender 
cord — the  yolk  stalk  (Fig.  123).  While  in  the  earlier  stages  there  is  an  active 
bending  of  the  margins  of  the  disk,  in  the  later  stages  the  body  grows  rapidly  in 
size,  especially  in  length,  and  extends  out  beyond  the  yolk  sac  (Fig.  120).  This 
makes  it  appear  that  the  yolk  stalk  is  becoming  smaller.  As  a  matter  of  fact, 
the  diminution  in  the  relative  size  of  the  yolk  stalk  is  more  apparent  than  real, 
the  apparent  diminution  being  caused  largely  by  the  rapid  increase  in  size  of  the 
embryonic  body  and  yolk  sac.  There  is,  however,  a  considerable  distance  where 
fusion  occurs  in  the  midventral  line  as  the  two  lateral  body  walls  meet  to  form 


142  TEXT-BOOK  OF  EMBRYOLOGY. 

the  ventral  body  wall.  This  line  of  fusion  is  significant  in  its  relation  to  certain 
malformations  (Chap.  XIX). 

Preceding  the  processes  which  establish  the  cylindrical  form  of  the  body, 
there  are  changes  in  the  relation  of  the  amnion  to  the  chorion.  Primarily,  the 
entire  dome-like  roof  of  the  amniotic  cavity  is  attached  to  the  chorion  (Fig.  90,  A). 
In  further  development,  however,  the  extraembryonic  mesoderm  between  the 
trophoderm  of  the  chorion  and  the  ectoderm  of  the  amnion  splits  farther  back 
over  the  embryo,  leaving  the  latter  attached  at  its  caudal  end  to  the  chorion  by  a 
mass  of  mesoderm — the  so-called  belly  stalk  (Figs.  90,  B,  and  85). 

Following  the  above  mentioned  changes  in  the  amnion,  chorion,  yolk  sac 
and  embryonic  disk,  the  amnion  continues  to  enlarge  and  thus  draws  the  belly 


Cephalic 
flexure 


Branchial  arches 
Branchial  grooves   ~ 
Heart 


Yolk  sac 

••^^^B^pr^*;.  & 

Dorsal  flexure 


FIG.  121. — Human  embryo  2.15  mm.  long.     His. 

stalk  under  the  embryonic  body  and  brings  it  closer  to  the  yolk  sac.  Finally,  as 
the  yolk  stalk  becomes  longer  and  more  slender,  the  belly  stalk  and  yolk  stalk 
unite  and  become  completely  surrounded  by  the  amnion.  There  is  thus  formed 
a  cord-like  structure — the  umbilical  cord — which  is  attached  to  the  ventral  side 
of  the  body  (Figs.  90,  D,  and  100;  see  also  p.  132). 

The  changes  which  occur  in  the  simple  cylindrical  body,  after  it  is  once 
formed,  consist  of  the  differentiation  of  the  head,  neck  and  body  regions  and  the 
development  of  the  extremities.  Even  in  Eternod's  embryo  (Fig.  119)  the 
cephalic  end  has  become  proportionately  larger  than  the  rest  of  the  body  and 
projects  somewhat  beyond  the  yolk  sac.  This  marks  the  beginning  of  the 


DEVELOPMENT  OF  THE  EXTERNAL  FORM  OF  THE  BODY.     143 

head.  The  extreme  end  of  the  head  region  is  bent  ventrally  almost  at  a  right 
angle  to  the  long  axis  of  the  body,  the  bend  being  known  as  the  cephalic  flexure. 
On  the  ventral  side  of  the  body  and  cranial  to  the  attachment  of  the  yolk  sac 
there  is  a  rather  large  protrusion  which  indicates  the  position  of  the  heart. 
Between  the  protrusion  and  the  bent  part  of  the  head  there  is  a  deep  depres- 
sion— the  oral  fossa.  A  series  of  bilaterally  symmetrical  structures  appear  in 
the  body  region  along  the  sides  of  the  neural  tube.  These  are  the  primitive 
segments  (mesodermic  somites). 

All  these  features  are  even  more  clearly  shown  in  Fig.  120,  which  represents 


Cephalic 
flexure 


Maxillary  process 


Oral  fossa 

Branchial  groove  I 

Branchial  arch  II  ^  A "  Mandibular  process 


Ventral  aortic  trunk 


Primitive 
segments 


Umbilical  vein 


Naso-frontal  process 


Belly  stalk 
Sacral  flexure 

FIG.  122. — Human  embryo  of  the  third  week.     His. 

an  embryo  2.5  mm.  in  length.  There  is  also  a  further  increase  in  the  size  of 
the  head  region.  A  distinct  concavity,  caused  by  the  dorsal  flexure,  is  seen  in 
the  dorsum  of  the  embryo. 

Another  embryo,  apparently  older  but  only  2.15  mm.  long,  shows  a  re- 
markable exaggeration  of  the  dorsal  flexure  (Fig.  121).  The  middle  part  of  the 
body  seems  to  be  drawn  ventrally  by  the  yolk  sac.  While  this  may  be  a 
normal  feature  at  this  stage,  it  soon  disappears  and  the  concavity  becomes  a 
convexity  (see  p.  144).  A  new  feature  also  appears  in  this  embryo  in  the  form 
of  two  vertical  depressions  just  caudal  to  the  head  region.  These  depressions 


144  TEXT-BOOK  OF  EMBRYOLOGY. 

represent  the  beginning  of  the  branchial  grooves  and  branchial  arches,  which  are 
exceedingly  important  in  the  development  of  the  face  and  neck  regions.  The 
branchial  arches  and  grooves  are  the  morphological  equivalents  of  the  gills 
and  gill  slits  in  lower  Vertebrates  (Fishes,  larvas  of  Amphibians). 

In  an  embryo  somewhat  further  advanced  (Fig.  122)  the  body  as  a  whole 
is  more  robust.  The  heart  is  more  prominent,  and  this  region  is  still  larger  in 
proportion  to  the  body  than  in  the  preceding  stages.  The  dorsal  flexure  is 
much  reduced.  The  cephalic  flexure  is  more  marked  than  in  the  preceding 
stages.  Two  other  flexures  have  appeared — the  cervical  flexure  just  caudal  to 
the  head  region,  the  sacral  flexure  near  the  caudal  end  of  the  body.  All  these 
flexures  together  make  the  embryo  as  a  whole  appear  crescentic  in  form.  The 
primitive  segments  are  at  the  highest  degree  of  their  development  and  extend 
from  the  cervical  flexure  to  the  caudal  end  of  the  body. 

The  two  vertical  depressions  in  the  head  region,  which  were  seen  in  the 
preceding  stage  (Fig.  121),  are  more  prominent  here  as  the  first  and  second 
branchial  grooves  or  clefts.  Just  caudal  to  these  two  other  similar  depressions 
appear  as  the  third  and  fourth  branchial  grooves.  Cranial  to  the  first  groove, 
between  the  first  and  second,  between  the  second  and  third,  and  caudal  to  the 
third  are  elevations  which  mark  the  first,  second,  third  and  fourth  branchial 
arches  respectively.  A  strong  process,  the  maxillary  process,  has  grown 
cranially  from  the  dorsal  part  of  the  first  arch.  The  main  part  of  the  arch  is 
the  mandibular  process. 

In  a  somewhat  later  stage  (Fig.  123)  further  distinct  changes  have  occurred, 
some  of  which  rather  than  leading  toward  the  adult  form  of  the  body  are  de- 
partures from  it.  For  example,  all  the  flexures  have  increased  to  such  an  extent 
that  the  tail  almost  touches  the  head,  the  entire  body  being  decidedly  concave  on 
the  ventral  side.  The  dorsal  flexure,  instead  of  forming  a  concavity  in  the  back, 
now  forms  a  distinct  convexity  and  gives  the  back  a  rounded  appearance.  As  a 
general  rule,  the  tail  at  this  stage  is  bent  to  the  right,  but  in  some  cases  the  bend 
is  toward  the  left. 

The  branchial  arches  and  grooves  are  especially  prominent.  The  fourth 
(and  last)  arch  has  appeared  and  caudal  to  this,  the  fourth  (and  last)  groove. 
The  first  three  arches  have  enlarged  and  become  elongated  so  that  they  almost 
meet  their  fellows  of  the  opposite  side  in  the  midventral  line.  The  site  of 
the  external  ear  is  marked  by  the  second  branchial  groove.  In  addition  to 
this,  the  anlagen  of  the  other  sense  organs  are  apparent.  The  optic  vesicle  is 
seen  just  cranial  to  the  dorsal  end  of  the  first  arch;  the  nasal  fossa  as  a  distinct 
depression  on  the  ventral  side  of  the  head  cranial  to  the  first  arch.  The  yolk 
sac  has  become  so  constricted  at  its  base  that  it  is  now  readily  divisible  into 
the  long,  slender  yolk  stalk  and  the  yolk  sac  or  vesicle. 

On  the  side  of  the  body,  just  caudal  to  the  cervical  flexure,  a  small  protu- 


DEVELOPMENT  OF  THE  EXTERNAL  FORM  OF  THE  BODY. 


145 


berance  forms  the  anlage  of  the  upper  extremity.  This  is  known  as  the  upper 
limb  bud.  A  similar  protuberance  caudal  to  the  sacral  flexure  is  the  lower  limb 
bud. 

Fig.  124  shows  a  stage  slightly  further  advanced  than  Fig.  1 23 .  The  embryo 
as  a  whole  is  more  stocky,  and  the  head  is  still  larger  in  proportion  to  the  rest 
of  the  body.  This  feature  is  especially  noticeable  from  this  stage  up  to  the 
time  of  birth.  The  sacral  and  cervical  flexures  are  still  very  prominent.  The 


Cervical  Cervical 

depression  flexure 


Dorsal  flex 


Branchial  arch  IV 
Branchial  groove  III 
Branchial  arch  III 
Branchial  groove  II 
Branchial  arch  II 
Branchial  groove  I 

Branchial  arch  I 

—  Mandibular  process 
Maxillary  process 
Eye 

—  Nasal  pit 


T }   Heart 


Yolk  stalk 


Lower  limb  bud 


Primitive  segments 


Upper  limb  bud         Liver         Sacral  flexure 
FIG.  123. — Human  embryo  with  twenty-seven  pairs  of  primitive  segments  (7  mm.,  26  days).     Mall. 


dorsal  flexure,  however,  is  less  prominent  and  the  body  of  the  embryo  is  more 
nearly  straight.  The  sacral  and  cervical  flexures  from  this  time  on  become 
more  and  more  reduced,  while  the  cephalic  flexure,  which  primarily  affects  the 
embryonic  brain,  persists  as  the  mid-brain  flexure  in  the  adult. 

The  branchial  arches  are  actually  no  smaller  but  appear  less  prominent. 
Between  the  mandibular  process  and  the  maxillary  process  there  is  a  distinct 
notch  which  corresponds  to  the  angle  of  the  mouth.  The  second  arch  has 
enlarged  at  the  expense  of  the  third  and  fourth,  has  grown  back  over  them  to  a 


146 


TEXT-BOOK  OF  EMBRYOLOGY. 


certain  extent  and  partially  hides  them.  The  nasal  fossa  is  deeper,  and  ex- 
tending from  it  to  the  optic  vesicle  is  a  groove — the  naso-optic  furrow- — which 
bounds  the  maxillary  process  on  the  cephalic  side. 

The  tail  (not  clearly  shown  in  the  figure)  is  proportionately  smaller.  It 
does  not  actually  diminish  in  size,  but  the  more  rapid  growth  of  the  body  makes 
it  appear  to  diminish.  The  limb  buds  are  larger  and  a  transverse  constriction 
divides  the  upper  into  a  proximal  and  a  distal  portion.  The  corresponding 
constriction  in  the  lower  limb  bud  has  not  yet  appeared.  The  protrusion  on  the 


Branchial  groove  III 

Branchial  arch  III 

Branchial  groove  II 

Branchial  arch  II 

Branchial  groove  I 

Mandibular  process 

Maxillary  process 

Eye 

Naso-optic  furrow 
Nasal  pit 


Yolk  sac 


Heart 


Lower         Liver 
limb  bud 


Upper        Umbilical        Yolk  stalk 
limb  bud          cord 


FIG.  124. — Human  embryo  with  28  pairs  of  primitive  segments  (7.5  mm.).     Photograph. 


ventral  side  of  the  body,  originally  caused  by  the  heart,  is  now  more  prominent 
owing  to  the  fact  that  the  rapidly  growing  liver  also  protrudes  ventrally.  In  this 
particular  case  the  yolk  sac  seems  unusually  large.  The  yolk  stalk  has  become 
enclosed  for  about  half  its  length  within  the  umbilical  cord. 

After  the  stage  just  described  the  dorsal  flexure  becomes  still  less  prominent, 
the  body  of  the  embryo  being  less  curved  (Fig.  125).  The  cervical  flexure 
remains  distinct,  so  that  the  head  is  bent  at  a  right  angle  to  the  long  axis  of  the 
body.  Two  slight  depressions  have  appeared  on  the  dorsum  of  the  embryo — 
the  occipital  depression  just  cranial  to  the  cervical  flexure,  the  cervical  depression 


DEVELOPMENT  OF  THE  EXTERNAL  FORM  OF  THE  BODY.      147 

just  caudal  to  the  cervical  flexure.  The  cervical  depression  becomes  more  con- 
spicuous in  later  stages  and  finally  persists  as  the  depression  at  the  back  of  the 
neck  in  the  adult. 

The  maxillary  process  is  more  prominent  than  in  the  preceding  stages,  as  is 
also  the  naso-optic  furrow.  The  second  arch  has  become  larger  and  has  grown 
over  the  third  and  fourth,  thus  completely  hiding  them,  but  a  depression  known 
as  the  precervical  sinus  is  left  just  caudal  to  the  second  arch.  The  first  branch- 
ial groove  is  relatively  large  and  marks  the  site  of  the  external  auditory  meatus, 
while  the  surrounding  portions  of  the  first  and  second  arches  in  part  are 
destined  to  give  rise  to  the  external  ear. 

Cervical  flexure 
Occipital  depression 


. 

Cephalic  flexure 

Dorsal  flexure 


Umbilical  cord 


Sacral  flexure 
FIG.  125. — Human  embryo  n  mm.  long  (31-34  days).     His 

The  distal  portion  of  the  upper  limb  bud  has  become  flattened,  and  four 
radial  depressions  mark  the  boundaries  between  the  digits.  The  lower  limb 
bud  is  now  divided  by  means  of  a  constriction  into  a  proximal  and  a  distal 
portion.  In  development  the  upper  limb  is  always  slightly  in  advance  of  the 
lower. 

The  rotundity  of  the  abdomen,  due  to  the  rapidly  growing  heart  and  liver, 
is  more  pronounced  than  in  the  preceding  stages. 

Fig.  126  shows  a  stage  in  which  the  crescentic  form  of  the  body,  as  seen  in 
profile,  is  not  so  apparent.  This  is*  due  principally  to  the  partial  straightening 
of  the  cervical  flexure  and  to  the  greater  rotundity  of  the  abdomen.  The 


148 


TEXT-BOOK  OF  EMBRYOLOGY. 


cervical  depression  is  deeper,  and  the  neck  region  in  general  is  fairly  well 
differentiated. 

The  ventral  part  of  the  first  branchial  arch  has  fused  with  the  ventral  part 
of  the  second,  leaving  the  dorsal  part  of  the  first  groove  open  to  form  the  ex- 
ternal auditory  meatus.  The  parts  surrounding  the  meatus  bear  more  resem- 
blance to  the  concha  of  the  ear.  The  mandibular  process  of  the  first  arch  has 
become  differentiated  in  part  into  the  lower  lip  and  chin  regions.  The  ventral 
(distal)  end  of  the  maxillary  process  represents  the  region  of  the  upper  lip.  The 


FIG.  126. 


FIG.  127. 


FIG.  126. — Human  embryo  of  15.5  mm.  (39-40  days).     His. 
FIG.  127. — Human  embryo  of  16  mm    (42-45  days,).     His. 

nose  is  apparent  as  a  short  process  extending  from  the  fore-brain  region  toward 
the  upper  lip. 

The  limb  buds  are  turned  more  nearly  at  right  angles  to  the  long  axis  of  the 
body.  The  radial  depressions  which  were  present  on  the  flattened  distal  por- 
tion of  the  upper  limb  in  the  preceding  stage  are  now  continuous  with  depres- 
sions around  the  distal  border.  Similar  radial  depressions  are  also  present  on 
the  distal  portion  of  the  lower  limb.  The  tail  is  smaller  in  proportion  to  the 
rest  of  the  embryo. 


DEVELOPMENT  OF  THE  EXTERNAL  FORM  OF  THE  BODY. 


149 


After  the  stage  shown  in  Fig.  126  the  cervical  flexure  continues  to  dimin- 
ish, so  that  the  head  comes  to  lie  nearly  in  a  direct  line  with  the  body  (Fig.  127). 
The  rotundity  of  the  abdomen  diminishes  owing  to  the  fact  that  the  heart  and 
liver  grow  more  slowly  relatively  to  the  body  as  a  whole.  The  tail,  which  was 
still  a  prominent  feature  in  Fig.  125,  continues  to  become  less  prominent  in  the 
succeeding  stages  (Figs.  127,  128,  129,  130).  This  is  not  due  so  much  to  an 
actual  atrophy  of  the  tail  as  to  an  increase  in  the  size  of  the  buttocks.  In  the 
adult  the  only  remnant  of  the  tail  is  the  coccyx. 


FIG.  128. 


FIG.  129. 


FIG.  130. 


FIG.  128. — Human  embryo  of  17.5  mm.  (47-51  days).  His. 
FIG.  129. — Human  embryo  of  18.5  mm.  (52-54  days).  His. 
FIG.  130. — Human  embryo  of  23  mm.  (2  months).  His. 


During  the  second  month  of  development  the  external  genitalia  become  very 
prominent  and  the  sexes  can  be  easily  differentiated. 

By  the  end  of  the  second  month  the  embryo  has  acquired  a  form  which 
resembles  in  a  general  way  the  form  of  the  adult  (Fig.  130).  From  this  time  on 
it  is  customary  to  speak  of  the  growing  organism  as  a.  foetus. 

Branchial  Arches — Face — Neck. 

At  a  very  early  stage  (embryos  of  2-4  mm.)  certain  peculiar  structures 
appear  in  that  part  of  the  embryo  which  is  destined  to  become  the  face  and  neck 
regions.  They  are  at  first  noticeable  as  slit-like  depressions  nearly  at  right 
angles  to  the  long  axis  of  the  body.  In  an  embryo  2.15  mm.  long  two  of  these 
depressions  are  visible  (Fig.  121).  Shortly  after  this  a  third  and  then  a  fourth 


150 


TEXT-BOOK  OF  EMBRYOLOGY. 


appears.  At  the  same  time  elevations  appear  between  the  succeeding  depres- 
sions, the  first  elevation  appearing  cranial  to  the  first  depression.  (Compare 
Figs.  122,  123.)  The  elevations  are  the  branchial  arches  and  the  depressions  are 
the  branchial  grooves.  Corresponding  elevations  and  depressions  also  mark  the 


FIG.  131. 


FIG.  132. 


FIG.  131. — Human  embryo  of  78  mm.  (3  months).     Minot. 
FIG.  132. — Human  embryo  of  155  mm.  (123  days).     Minot. 

interior  of  the  pharynx,  so  that  the  portions  of  the  wall  of  the  pharynx  which 
correspond  to  the  grooves  are  thin  as  compared  with  those  portions  which  cor- 
respond to  the  arches. 

The  arches  develop  in  order  from  the  first  to  the  fourth;  consequently  they 
are  successively  smaller  from  the  first  to  the  fourth  (Fig.  122).     The  conditions 


DEVELOPMENT  OF  THE  EXTERNAL  FORM  OF  THE  BODY.     151 

change  rapidly,  so  that  in  embryos  of  9-10  mm.,  the  third  and  fourth  arches  have 
sunk  inward,  thus  producing  a  depression  known  as  the  precervical  sinus. 
Soon  after  this  the  second  arch  enlarges,  grows  over  the  sinus,  and,  fusing  with 
the  underlying  arches,  fills  up  the  depression. 

The  ventral  end  of  the  first  arch  fuses  with  the  ventral  part  of  the  second 
across  the  ventral  part  of  the  first  groove.  The  dorsal  part  of  the  first  groove  is 
thus  left  open  and  becomes  the  external  auditory  meatus.  A  part  of  the  second 
arch,  together  with  a  part  of  the  first  arch  bounding  the  first  groove  on  the 
cranial  side,  is  transformed  into  the  concha  of  the  ear  (Figs.  123,  125,  126). 

The  first  branchial  arch  becomes  the 
largest  and  undergoes  profound  changes 
which  are  extremely  important  in  the  de- 
velopment of  the  face  region.  Earlier  in 
this  chapter  (p.  143)  it  was  stated  that  the 
cephalic  flexure  caused  the  fore-brain  to 
project  ventrally  at  a  right  angle  to  the  long 
axis  of  the  body,  and  that  between  the  pro- 
jecting fore-brain  and  the  heart  a  distinct 
depression  or  pit — the  oral  fossa — was  pres- 
ent. Soon  after  the  appearance  of  the  first 
arch  a  strong  process — the  maxillary  process 
— develops  on  its  cranial  side  (Fig.  122). 
The  main  portion  of  the  arch,  which  may 
be  now  called  the  mandibular  process, 
rapidly  increases  in  size,  extends  ventrally 
and  finally  meets  and  fuses  with  its  fellow 
of  the  opposite  side  in  the  midventral  line 
(Fig.  134).  The  result  of  the  enlargement 
of  the  first  arch  and  its  process  is  that  they 

.    A  ,   !  ,11  11        FIG.   133. — Human  embrvo  of  4  months. 

are  interposed  between  the  heart  and  the  Natural  size.    Koiimann. 

fore-brain  vesicle,  thus  bounding  the  oral 

fossa  laterally  (Fig.  122).  During  this  time  the  heart  is  gradually  moving 
caudally.  Meanwhile  a  process — the  naso-frontal  process — grows  ventrally 
from  the  medial  portion  of  the  fore-brain  region  and  comes  in  contact  laterally 
with  the  maxillary  process.  Along  the  line  of  contact  a  furrow  is  left,  which 
extends  obliquely  to  the  region  of  the  optic  vesicle  and  is  known  as  the  naso- 
optic  furrow  (Fig.  134). 

The  various  structures  which  have  been  mentioned  bound  the  oral  fossa 
which  has  become  a  deep  quadrilateral  pit.  Cranially  (above)  the  fossa  is 
bounded  by  the  broad,  rounded,  unpaired  naso-frontal  process;  caudally  (below) 
it  is  bounded  by  the  mandibular  processes;  laterally  it  is  bounded  by  the  maxil- 


152  TEXT-BOOK  OF  EMBRYOLOGY. 

lary  processes,  and  to  a  slight  extent  by  the  mandibular  processes.  Between 
the  maxillary  and  mandibular  processes  on  each  side  a  notch  marks  the  angle 
of  the  mouth. 

As  development  proceeds  these  structures  become  more  elaborate  and  enter 
into  more  intimate  relations  with  one  another.  The  naso-frontal  process 
extends  farther  downward  toward  the  mandibular  processes,  so  that  the 
oral  fossa  becomes  more  nearly  enclosed  and  the  entrance  to  it  reduced  to  a 
crescent-shaped  slit — the  mouth  slit.  At  the  same  time  two  secondary  processes 
develop  on  each  side  from  the  naso-frontal  process.  One  of  these — the 
medial  nasal  process — forms  near  the  medial  line;  the  other — the  lateral  nasal 
process — forms  more  laterally  (Figs.  135, 136).  Between  the  two  processes  there 


Cerebral  hemisphere 

Lat.  nasal  process 

Nasal,.- •£_«?'  m-   Eye 

Med.  nasal  process  -"^HIHMI^Bll^L  JH          Naso-optic  furrow 

Maxillary  process 
Angle  of  mouth  ^"f 

Mandibular 


FIG.  134. — Ventral  view  of  head  of  8  mm.  human  embryo.     His. 


is  a  depression — the  nasal  pit — which  marks  the  entrance  to  the  future  nasal 
cavity.  The  maxillary  process  on  each  side  grows  farther  toward  the  medial 
line  and  comes  in  contact  with  the  lateral  and  medial  nasal  processes. 

At  this  stage  all  the  elements  which  enter  into  the  fundamental  structure  of 
the  face  region  are  present.  Further  development  consists  essentially  of 
fusions  between  these  various  elements. 

The  two  medial  nasal  processes  come  closer  together  to  form  the  single 
medial  process  which  gives  rise  to  the  medial  portion  of  the  upper  lip  and  to  the 
adjoining  portion  of  the  nasal  septum.  The  maxillary  process  on  each  side 
fuses  with  the  corresponding  lateral  and  medial  nasal  processes.  This 
fusion  obliterates  the  naso-optic  furrow  and  also  shuts  off  the  communi- 
cation between  the  mouth  slit  and  the  nasal  pit  (Figs.  136,  137).  The  lateral 
nasal  process  gives  rise  to  the  wing  of  the  nose;  the  maxillary  process  gives  rise 


DEVELOPMENT  OF  THE  EXTERNAL  FORM  OF  THE  BODY.     153 

to  the  major  part  of  the  cheek  and  the  lateral  portion  of  the  upper  lip.  The 
fusion  between  the  maxillary  and  nasal  processes,  as  seen  on  surface  view,  is 
coincident  with  and  a  part  of  the  separation  of  the  nasal  cavity  from  the  oral 
cavity  (see  page  320).  The  nose  itself  is  at  first  a  broad,  flat  structure,  but 
later  becomes  elevated  above  the  surface  of  the  face,  with  an  elongation  and  a 
narrowing  of  the  bridge. 


Mid-brain 


Cerebral  hemisphere 


Lat.  nasal  process " 

__  "~~  '    I'VC 

— -"^^"S^-  ^^      •  Naso-optic  furrow 

— •"  *.*f9T  ^U*.  '*' 

Med.  nasal  process 

^|      j**'  .  ->>^      ^f-.'  ^A      Maxillary  process 

Angle  of  mouth '     x 

• —  Mandibular  process 

HI —  Branchial  grooves 
Branchial  arch  II 


FIG.  135. — Ventral  view  of  head  of  113  mm.  human  embryo.     Rabl. 

The  lower  jaw,  lower  lip  and  chin  are  formed  by  the  mandibular  processes  of 
the  first  branchial  arch  (Figs.  134,  136,  137).  At  first  the  chin  region  is  rela- 
tively short,  but  broad  in  a  transverse  direction.  Later  it  becomes  longer  and  a 
transverse  furrow  divides  the  middle  portion  into  lower  lip  and  chin  (Fig.  137). 

The  Extremities. 

The  limb  buds  appear  in  human  embryos  about  the  end  of  the  third  week  as 
small,  rounded  protuberances  on  the  ventro-lateral  surface  of  the  body.  The 
upper  limb  buds  arise  just  caudal  to  the  level  of  the  cervical  flexure,  the  lower 
opposite  the  sacral  flexure  (Figs.  123,  124).  The  upper  appear  first,  the  lower 
following  shortly,  and  the  difference  in  time  in  the  appearance  of  the  upper 
and  lower  buds  is  followed  by  a  difference  in  degree  of  development,  the 
upper  extremities  maintaining  throughout  fcetal  life  a  slight  advance  in  develop- 
ment over  the  lower. 


154 


TEXT-BOOK  OF  EMBRYOLOGY. 


During  the  fourth  week  the  limb  buds  become  elongated,  and  each  bud 
becomes  divided  by  a  transverse  constriction  into  a  proximal  and  a  distal  por- 
tion (Figs.  124,  125).  The  proximal  portion  remains  cylindrical,  while  the 


Nasa  fossa 


Naso-optic  furrow  ~—g 
Mouth  slit 


/ 


Branchial  groove  I ' 


V 


Cerebral  hemisphere 


^— Naso-frontal  process 

_- Lateral  nasal  process 

— Medial  nasal  process 

Maxillary  process 

Mandibular  process 


FIG.  136. — Ventral  view  of  head  of  13.7  mm.  human  embryo.     His. 

distal  portion  becomes  somewhat  broader  and  considerably  flattened.  Dur- 
ing the  fifth  week  the  digits  appear  (see  below).  During  the  sixth  week  the 
proximal  portion  of  each  bud  is  subdivided  by  a  transverse  constriction  into 
two  segments  (Fig.  127).  Thus  each  extremity  as  a  whole  is  divided  into  three 


Branchial  groove  I" 
(external  ear) 


Nose 

.  Lat.  nasal  process 
Maxillary  process 

Med.  nasal  process 


FIG.  137. — Ventral  view  of  head  of  human  embryo  of  8  weeks.     His. 

segments — each  upper,  into  arm,  forearm  and  hand,  each  lower,  into  thigh,  leg 
and  foot. 

The  anlagen  of  the  digits  (fingers  and  toes)  appear,  during  the  fifth  week,  in 
the  broader,  flattened  distal  portions  of  the  limb  buds.     The  boundaries  be- 


DEVELOPMENT  OF  THE  EXTERNAL  FORM  OF  THE  BODY.      155 

tween  the  anlagen  are  marked  by  radial  depressions  on  the  flat  surfaces;  the 
anlagen  themselves  are  the  elevations  between  the  depressions  (Figs.  125,  126). 
The  anlagen  grow  rapidly  in  thickness  and  length,  thus  producing  not  only  an 
apparent  deepening  of  the  radial  depressions  but  also  indentations  around  the 
distal  free  borders  of  the  limb  buds  (Fig.  126).  The  depressed  areas  produce  a 
web-like  structure  between  the  digits,  resembling  the  web  in  some  aquatic 
animals.  The  web  does  not  keep  pace  with  the  digits,  however,  and  is  soon 
confined  to  the  proximal  ends  of  the  latter.  In  length  the  fingers  grow  slightly 
more  rapidly  than  the  toes  and  thus  become  somewhat  longer.  From  the 
seventh  week  on,  the  thumb  and  great  toe  become  more  and  more  widely  sepa- 
rated from  the  index  finger  and  the  second  toe  respectively  (Figs.  128,  130,  131). 

As  the  limb  buds  become  elongated  during  the  earlier  stages  of  development, 
they  assume  a  position  with  their  long  axes  nearly  parallel  with  the  long  axis  of 
the  body,  and  are  directed  caudally  (Fig.  125).  In  later  stages  they  are  directed 
ventrally  and  their  long  axes  are  nearly  at  right  angles  to  the  long  axis  of  the 
body  (Fig.  126).  The  radial  margins  of  the  upper  extremities  are  turned 
toward  the  head,  as  are  the  tibial  margins  of  the  lower.  The  palmar  surfaces 
of  the  hands  and  the  plantar  surfaces  of  the  feet  are  turned  inward  or  toward 
the  body.  The  elbow  is  turned  slightly  outward  and  toward  the  tail,  the  knee 
slightly  outward  and  toward  the  head.  From  these  conditions  it  may  be  con- 
cluded that  the  radial  side  of  the  upper  extremity  is  homologous  with  the  tibial 
side  of  the  lower;  that  the  palmar  surface  of  the  hand  is  homologous  with  the 
plantar  surface  of  the  foot;  and  that  the  elbow  is  homologous  with  the  knee. 

In  order  to  acquire  the  position  relative  to  the  body  as  found  in  postnatal 
life,  the  extremities  must  undergo  further  changes.  These  consist  essentially 
of  tortions  around  their  long  axes.  The  right  upper  extremity  turns  to  the 
right,  the  right  lower  turns  to  the  left.  The  left  upper  extremity  turns  to  the 
left,  the  left  lower  turns  to  the  right.  At  the  same  time  the  extremities  rotate 
through  an  angle  of  ninety  degrees  and  again  come  to  lie  parallel  with  the  long 
axis  of  the  body.  The  result  is  that  the  radial  sides  of  the  upper  extremities  are 
turned  outward  (away  from  the  sagittal  plane  of  the  body)  and  the  tibial  sides 
of  the  lower  are  turned  inward  (toward  the  sagittal  plane  of  the  body).  In  the 
upper  extremity  this  is,  of  course,  the  supine  position  in  which  the  radius  and 
ulna  are  parallel. 

Age  and  Length  of  Embryos. 

AGE. — Certain  general  conclusions  regarding  the  age  of  embryos  have  been 
formulated  by  His  (Anatomic  menschlicher  Embryonen,  1882)  and  accepted 
for  the  most  part  by  embryologists.  These  as  stated  by  His  are  as  follows : 

i.  Development  begins  at  the  time  of  impregnation,  that  is,  at  the  moment 
when  the  male  sexual  element  enters  the  ovum  and  fertilizes  it. 


156  TEXT-BOOK  OF  EMBRYOLOGY. 

2.  The  time  the  ovum  leaves  the  ovary  is  determined  by  the  menstrual 
period,  but  the  rupture  of  the  (Graafian)  follicle  is  not  necessarily  coincident 
with  the  beginning  of  hemorrhage;  it  may  occur  two  or  three  days  before  or  it 
may  occur  during  hemorrhage. 

3.  The  egg  is  not  capable  of  being  fertilized  at  any  point  in  its  course  from 
the  ovary  to  the  uterus,  but  only  in  the  upper  part  of  the  oviduct. 

4.  The  spermatozoa  which  have  entered  the  female  sexual  organs  must 
await  the  ovum  in  the  upper  part  of  the  oviduct,  and  can  retain  their  vitality 
here  for  several  days  or  possibly  for  several  weeks;  the  time  of  cohabitation, 
therefore,  does  not  stand  in  direct  relation  to  the  age  of  the  embryo. 

5.  In  the  majority  of  cases  the  age  of  the  embryo  can  be  estimated  from  the 
beginning  of  the  first  menstrual  period  which  has  lapsed.     It  is  possible,  how- 
ever, for  menstruation  to  occur  after  fertilization  of  the  ovum. 

6.  The  age  of  the  embryo  can  be  expressed  thus :  age  =  X  — M,  or  age  = 
X  — M  — 28.  X  is  the  date  of  the  abortion  and  M  is  the  beginning  of  the  last 
menstrual  period.     The  second  formula  is  used  where  it  is  necessary  to  estimate 
from  the  beginning  of  the  first  period  which  has  lapsed. 

There  is  no  doubt  whatever  that  the  age  of  the  embryo  must  be  dated  from 
the  time  of  fertilization  of  the  ovum;  but  owing  to  the  fact  that  the  time  of 
fertilization  of  the  human  ovum  is  not  known,  the  exact  age  cannot  be  deter- 
mined. Even  when  the  date  of  coitus  and  the  time  of  cessation  of  the  menses 
are  known,  the  uncertainty  regarding  the  time  of  ovulation  and  the  time  re- 
quired by  the  spermatozoa  to  reach  the  upper  end  of  the  oviduct  must  be 
taken  into  consideration.  It  is  now  generally  conceded  that  ovulation  and 
menstruation  are  coincident  in  the  majority  of  cases,  but,  on  the  other  hand, 
ovulation  is  known  to  occur  sometimes  independently  of  the  menstrual  periods 
(see  also  p.  30). 

In  addition  to  the  uncertainty  regarding  the  time  when  development 
begins  there  is  also  an  uncertainty  as  to  the  time  when  the  embryo  ceases  to 
develop.  For  in  most  cases  the  embryos  are  abortions  and  the  death  of  the 
embryo  does  not  necessarily  precede  immediately  its  expulsion  from  the  uterus. 

It  is  convenient,  however,  for  practical  purposes,  to  have  some  means  of 
approximating  the  age  of  an  embryo.  His'  formulae  serve  to  determine  the  age 
within  certain  limits.  It  is  obvious  from  these  formulas  that  there  is  a  possibility 
of  an  error  of  twenty-eight  days  in  the  estimate.  Yet  in  the  earlier  stages  of 
development  (during  the  first  three  months)  the  error  can  be  corrected  after 
examination  of  the  embryo,  since  there  is  no  difficulty  in  recognizing  the  differ- 
ence, for  example,  between  an  embryo  two  weeks  old  and  one  six  weeks  old. 

LENGTH. — ]\/Iany  German  authors  employ  two  different  methods  for 
measuring  embryos  at  different  periods.  One  of  these  methods  they  use 
in  measuring  embryos  between  4  and  14  mm.,  when  the  body  is  much  curved. 


DEVELOPMENT  OF  THE  EXTERNAL  FORM  OF  THE  BODY.     157 

The  length  of  the  embryo  is  considered  as  the  length  of  a  straight  line  drawn 
from  the  apex  of  the  cervical  flexure  to  the  apex  of  the  sacral  flexure  (neck- 
rump  length,  Nackensteisslange;  see  Fig.  124).  During  the  second  month  and 
later,  or  in  embryos  of  more  than  20  mm.,  the  body  becomes  more  nearly 
straight  and  the  measurement  is  taken  along  a  straight  line  from  the  apex  of  the 
cephalic  flexure  to  the  apex  of  the  sacral  flexure  (crown-rump  length,  Scheitel- 
steisslange;  see  Fig.  126). 

Owing  to  the  changes  in  curvature  of  embryos  during  development,  no 
one  system  of  measurement  will  give  uniform  results  for  all  stages.  In  this 
country  it  is  the  general  practice  to  measure  the  greatest  length  of  the  embryo, 
in  its  natural  attitude,  along  a  straight  line.  The  measurement  does  not 
of  course  include  the  extremities.  At  certain  stages  this  length  corresponds 
with  the  neck-rump  length,  at  other  stages  with  the  crown-rump  length,  at  still 
other  stages  with  neither. 

RELATION  OF  AGE  TO  LENGTH. — Not  infrequently  the  history  of  an  embryo 
is  not  obtainable,  and  in  such  cases  the  age  must  be  inferred  from  what  is  known 
concerning  the  relation  of  the  age  to  the  length  of  the  embryo.  The  age  can  be 
computed  approximately  by  this  means,  although  there  is  a  possibility  of  error. 
Embryos  of  the  same  age  are  not  necessarily  of  the  same  length,  since  conditions 
of  nutrition,  etc.,  determine  not  only  the  size  of  the  embryo  but  also  the  degree 
of  its  development.  In  the  later  stages  of  development  the  limit  of  error  is  not 
so  important,  but  in  the  younger  stages  the  difference  of  a  day  or  two  means 
much. 

His  estimated  the  ages  of  a  number  of  embryos  from  available  data  as 
follows : 

Embryos  of  2-2^  weeks  measure  2.2-3  mm-  (neck-rump  length). 

Embryos  of  2^-3  weeks  measure  3-4.5  mm.  (neck-rump  length). 

Embryos  of  3^  weeks  measure  5-6  mm.  (neck-rump  length). 

Embryos  of  4  weeks  measure  7-8  mm.  (neck-rump  length). 

Embryos  of  4^  weeks  measure  10-11  mm.  (neck-rump  length). 

Embryos  of  5  weeks  measure  13  mm.  (neck-rump  length). 

More  recent  researches  on  the  rate  of  development  in  the  lower  Mammals 
tend  to  show  that  development  proceeds  relatively  slowly  during  the  earliest 
stages,  and  then  goes  on  with  increasing  rapidity  for  a  time.  In  the  rabbit,  for 
example,  it  has  been  shown  that  the  embryonic  disk  is  but  slightly  differentiated 
at  the  seventh  and  eighth  days,  while  at  the  tenth  day  the  embryo  possesses 
branchial  grooves  and  primitive  segments.  If  this  peculiarity  in  the  rate  of 
development  occurs  in  the  human  embryo,  the  ages  assigned  to  the  earlier 
embryos  by  His  must  be  increased. 

Mall's  formula  for  estimating  age,  deduced  from  observations  on  a  large 
number  of  embryos,  are  as  follows:  In  embryos  of  i-ioo  mm.  the  age  in  days 


158 


TEXT-BOOK  OF  EMBRYOLOGY. 


can  be  expressed  fairly  accurately  by  the  square  root  of  the  length  multiplied  by 
100  (-\ /length  in  mm.  x  100).  In  embryos  between  100  and  220  mm.  the  age 
in  days  is  about  the  same  as  the  length  in  millimeters. 

Some  of  the  most  important  embryos  which  have  been  described  are 
listed  in  the  accompanying  table,  no  pretense  being  made  of  giving  a  complete 
list.  The  table  is  compiled  largely  from  the  more  extensive  tables  of  Mall 
and  merely  serves  to  indicate  some  of  the  younger  embryos  with  fairly  well- 
known  histories,  from  which  certain  conclusions  have  been  drawn  concerning 
the  relation  of  age  to  length.  The  periodicals  in  which  descriptions  may  be 
found  are  given  with  the  authors'  names  in  "References  for  Further  Study" 
at  the  end  of  this  chapter. 


No. 

Observer 

Dimensions    of    chori- 
onic  vesicle  in 
millimeters 

Number 
of  days  be-    Number  of  days 
tween  last       between  first 
menstrual       lapsed  period 
period  and       and  abortion 
abortion 

Probable 

age  in  days 

Length  of 
embryo  in 
millimeters 

i 

2 

3 

6 

7 
8 

9 
10 
ii 

12 
13 
14 

15 

16 

J7 
18 

19 

20 
21 

22 

23 
24 

25 
26 

Bryce-Teacher 
Leopold 

1.9  x  i.i  x  .95  

?8.  . 

10  

13-14...  . 

0.15  

i  4  x   9  x   8 

Peters  
Reichert  
von  Spec  
Mall  
Eternod  
von  Spec  .  ... 

3-  x  1.5x1.5  
5-5x3-3  
7-Sx5-5  
10.5  x  7.  x  7  
10.8  x  8.2  x  6  
10x85x65 

3°  
42  
35  
4i  
34  

•1C 

14  
13  

14  

12  
13  

12    

0.19  

o-37  
0.8  

J-3  

I.C4  . 

Mall  

18.  x  18x8  

41  

13  

1^  

2.1  

Thomson  
His 

5-7  

I  C  X  I  2   5 

42  

4O 

14  

I  2 

U  

T  9. 

2.1  
2  If. 

Thomson  
von  Spee  .... 

I5XIO  

14.  . 

14  

2.Z..  . 

i5XI4  
8  
14  x  ii  
24  x  16  x  9 

42  
43  
48  

A  7 

14  i     14  

15     15  
2O  2O  
T/l      

2.69  

3  

3-2  

A  .  . 

Janosik  
His  
Mall 

His 

?O  X  2s                                                Cl 

27                        4.  . 

His  

2  C  X  2O 

21  .   . 

21.  .               .       Z.  . 

Mever  

22.                l8     

18.  .      ...     5.2  

Stubenrauch  . 

A  e     

17    . 

17..              .      6.. 

Mall  
His  
Mever 

25  x  25  

21  X  17  

At 

52  

57  
28 

24  

*>(?)  

24  7  

27  7-75  
28..  .        .    8  

Ecker  
His  

30  x  27  

35X28  

60  
61  
61  

32  

33  
35  

32  10  
33  «  
35   13-6  

His  

Normal,  Abnormal  and  Pathological  Embryos. 

In  the  majority  of  cases  of  spontaneous  abortion  it  is  not  possible  to  examine 
the  uterus;  but  in  those  cases  where  it  is  possible,  examination  frequently  shows 
abnormal  or  pathological  conditions.  As  might  be  expected,  the  embryos 
obtained  from  abnormal  or  pathological  uteri  very  frequently  show  anom- 
alous conditions  or  pathological  changes,  or  both.  Since  many  of  the 


DEVELOPMENT  OF  THE  EXTERNAL  FORM  OF  THE  BODY.      159 

human  embryos  obtained  are  the  results  of  spontaneous  abortions,  there  is 
reason  to  suspect  that  such  embryos  are  not  normal.  To  the  physician,  as 
well  as  to  the  embryologist,  it  is  important,  therefore,  that  there  should  be  some 
criteria  for  differentiation  between  normal  and  abnormal  or  pathological 
embryos. 

Gross  anomalies,  or  monstrosities,  such  as  cases  in  which  the  head  or  some 
other  member  of  the  body  is  lacking,  or  in  which  the  head  is  disproportionately 
large  or  disproportionately  small,  or  in  which  two  embryos  are  directly  united, 
or  in  which  the  foetal  membranes  are  partially  lacking,  or  in  which  the  mem- 
branes are  present  and  the  embryo  wholly  or  partially  lacking,  and  many  other 
anomalous  conditions,  can,  of  course,  be  recognized  at  once.  Extensive 
pathological  changes  or  processes  of  disintegration  in  the  tissues  of  the  em- 
bryo or  fcetal  membranes  are  also  easily  recognized.  But  there  are  many  less 
obvious  anomalies  and  pathological  conditions  which,  nevertheless,  are  im- 
portant. Such  cases  are  most  difficult  to  differentiate. 

The  fcetal  membranes  not  infrequently  are  useful  in  determining  whether 
an  embryo  has  followed  the  normal  course  of  development.  During  the  first 
month  the  amnion  invests  the  embryo  rather  closely  when  development  is 
normal.  If  the  amniotic  sac  is  disproportionately  large,  however,  it  is  a  mark 
of  abnormal  or  pathological  changes.  In  some  cases  an  amniotic  sac  50  to  60 
mm.  in  diameter  contains  an  embryo  but  a  few  millimeters  in  length.  In  the 
earlier  stages  of  development,  before  the  amnion  enlarges  sufficiently  to  reach 
the  chorion,  there  is  present  a  delicate  network  of  fibrils,  the  magma  reticulare, 
which  is  attached  to  both  chorion  and  amnion  and  which  serves  as  a  sort  of 
anchor  for  the  amnion.  In  abnormal  or  pathological  cases  the  magma  reticu- 
lare  may  become  wholly  or  partially  fluid  or  granular,  or  may  become  greatly 
increased  in  amount.  It  may  even  extend  through  the  amnion  and  reach  the 
embryo  itself. 

Normal  human  as  well  as  other  mammalian  embryos  in  the  fresh  condition 
are  more  or  less  transparent,  and  such  structures  as  the  heart,  the  larger  blood 
vessels,  the  liver,  and  the  brain  vesicles  can  be  seen  through  the  skin.  If  the 
embryo  has  been  dead  for  some  time  or  has  undergone  pathological  or  degen- 
erative changes,  the  transparency  is  lost. 

Where  pathological  or  degenerative  changes  in  the  embryo  or  its  membranes 
are  suspected  but  cannot  be  definitely  determined  by  macroscopic  examination, 
recourse  may  be  had  to  sectioning  and  staining. 

PRACTICAL  SUGGESTIONS. 

Since  the  earlier  stages  of  human  embryos  in  any  condition  are  not  readily  procured,  all 
embryos  which  come  into  the  hands  of  physicians  or  others  should  be  preserved  and  turned 
over  to  someone  who  can  use  them  in  the  study  of  development.  Abnormal  or  pathological 


160  TEXT-BOOK  OF  EMBRYOLOGY. 

embryos  are  often  extremely  valuable,  for  many  anomalous  conditions  in  postnatal  life 
can  be  explained  on  the  ground  of  unnatural  developmental  conditions.  Obstetricians  and 
gynecologists  can  render  great  service  to  embryology  by  saving  curettings  or  the  entire  uterus 
in  cases  where  pregnancy  is  suspected  or  known  to  occur  and  turning  them  over  to  a  com- 
petent embryologist.  The  earliest  stages  are  especially  valuable.  Never  should  a  human 
embryo,  normal  or  abnormal,  under  any  circumstances  be  thrown  away. 

When  the  uterus  is  removed  where  there  is  suspected  pregnancy,  it  should  always  be  saved. 
Within  as  short  a  time  as  possible,  carefully  open  the  uterus  by  a  ventral  median  incision. 
If  pregnancy  has  gone  beyond  the  first  month,  the  membranes  and  embryo  are  easily  seen. 
During  the  earliest  stages  of  pregnancy,  especially  during  the  first  part  of  the  first  month 
it  is  sometimes  very  difficult  to  locate  the  embryo  in  the  uterus.  The  most  likely  position 
is  on  the  dorsal  wall.  It  may  show  only  as  a  scarcely  visible  elevation  in  the  mucous  mem- 
brane. If  the  little  elevation  is  once  recognized,  cut  out  the  block  of  uterine  wall  containing 
it.  Fix  the  block  in  some  good  fluid,  such  as  Orth's  fluid  and  embed  carefully  in  paraffin. 
Cut  serial  sections  at  right  angles  to  the  inner  surface  of  the  uterine  mucosa.  The  sections 
may  be  stained  as  desired,  Weigert's  hasmatoxylin  and  eosin  giving  good  results  (see 
Appendix) .  The  most  valuable  human  embryos  in  the  earliest  stages  have  all  been  obtained 
in  a  similar  manner. 

Embryos  three  to  eight  weeks  old  may  be  fixed  with  the  membranes  intact.  Put  the 
specimen  in  a  large  quantity  of  strong  alcohol  (the  alcohol  of  druggists  is  never  too  strong). 
The  volume  of  the  alcohol  should  be  at  least  ten  times  the  volume  of  the  specimen.  A  4 
per  cent,  solution  of  formalin  (one  volume  of  the  commercial  formalin — which  is  a  40  per 
cent,  solution  of  formaldehyde  gas  in  water — to  nine  volumes  of  water)  may  be  used  if  alcohol 
cannot  be  obtained  at  once.  The  specimen  should  not  be  left  in  formalin,  however,  longer 
than  a  few  days,  for  it  is  likely  to  become  somewhat  blackened  owing  to  changes  in  the  blood. 
As  soon  as  possible,  it  should  be  put  in  Orth's  fluid  for  a  day  or  two,  and  then  put  through 
graded  alcohols  up  to  80  per  cent.  Kleinenberg's  mixture  is  also  an  excellent  fixative  for 
young  embryos. 

In  embryos  eight  to  twelve  weeks  old  the  membranes  should  be  opened  before 
fixing.  Strong  alcohol  may  be  used  as  a  fixative,  as  in  the  earlier  stages,  but  usually  causes 
considerable  shrinkage.  A  better  plan  is  to  put  the  embryo  in  Orth's  fluid  for  a  few 
days,  the  length  of  time  depending  upon  the  size  of  the  embryo,  and  then  to  put  it 
through  the  graded  alcohols  up  to  80  per  cent.  As  mentioned  in  the  preceding  paragraph, 
4  per  cent,  formalin  may  be  used  as  a  fixative,  but  should  be  followed  in  a  few  days  by  Orth's 
fluid  and  the  graded  alcohols.  Zenker's  fluid  is  frequently  used  as  a  fixative  for  embryos 
but  always  causes  some  shrinkage.  Aside  from  the  shrinkage,  it  gives  very  good  results. 
(See  Appendix.) 

If  embryos  of  twelve  weeks  or  more  are  to  be  studied  histologically,  they  should  be 
opened  by  a  ventral  medial  incision  before  fixing.  It  is  well  also  to  make  a  few  incisions 
in  the  skull.  If  it  is  desired,  organs  or  parts  of  organs  may  be  removed  and  fixed  by  them- 
selves. Orth's  or  Zenker's  fluid  may  be  used  with  good  results. 

For  gross  preparations,  embryos  may  be  fixed  as  suggested  in  the  .preceding  paragraphs. 
Then,  if  occasion  requires,  they  can  be  studied  histologically  at  a  later  period.  Gross 
preparations  which  are  not  likely  to  be  used  histologically  can  be  fixed  and  preserved  indefi- 
nitely in  4-10  per  cent,  formalin,  with  practically  no  shrinkage,  although  there  is  a  possi- 
bility of  discoloration  due  to  changes  in  the  blood. 

As  complete  histories  as  possible  of  all  embryos  should  be  obtained  and  recorded.  The 
younger  stages  should  always  be  carefully  measured  before  fixing.  It  is  also  advisable  to 


DEVELOPMENT  OF  THE  EXTERNAL  FORM  OF  THE  BODY.      161 

have  the  embryos  photographed.  In  short,  all  possible  data  concerning  an  embryo  should 
be  obtained,  not  only  for  use  in  studying  it  as  an  individual  but  also  for  use  in  comparing  it 
with  other  embryos. 

Models  of  embryos  can  be  made  from  serial  sections  by  means  of  the  wax  reconstruction 
method.  (See  Appendix.) 

For  class  study  on  the  external  form  of  the  body,  very  useful  preparations  can  be  made 
by  mounting  whole  small  pig  embryos  or  parts  of  embryos  in  glycerin  jelly  in  small  flat 
dishes.  The  dishes  can  be  sealed  and  handled  freely. 

References  for  Further  Study. 

VAN  BENEDEN,  E. :  Recherches  sur  les  premiers  stades  du  developpement  du  Murin  (Ves- 
pertilio  murinus).  Anal.  Anz.,  Bd.  XVI,  1899. 

BRYCE,  T.  H.,  and  TEACHER,  J.  H.:  An  Early  Human  Ovum  Imbedded  in  the  Decidua. 
Mac  Lehose  &  Sons,  Glasgow,  1908. 

ECKER,  A.:  Beitrage  zur  Kenntniss  der  ausseren  Formen  jiingster  menschlichen  Embryo- 
nen.  Archiv.  j.  Anat.  u.  Physiol.,  Anat.  Abth.,  1880. 

ETERNOD,  A.  C.  F.:  Communication  sur  un  oeuf  avec  embryon  excessivement  jeune. 
Arch.  ital.  de  Biol.  Suppl.  12  et  14,  1894. 

ETERNOD,  A.  C.  F.:  Sur  un  oeuf  humain  de  16.3  mm.  avec  embryon  de  2.1  mm.  Arch, 
des.  sci.  phys.  et  nat.,  Vol.  II,  1896. 

His,  W.:  Anatomic  menschlicher  Embryonen.     With  Atlas.    1880-1885. 

His,  W. :  Die  Entwickelung  der  menschlichen  und  tierischen  Physiognomien.  Arch.  /. 
Anat.  u.  Physiol.,  Anat.  Abth.,  1892. 

jAN6siK,  J.:  Zwei  junge  menschliche  Embryonen.     Arch.  /.  mik.  Anat.,  Bd.  XXX,  1887. 

KEIBEL,  F.:  Ein  sehr  junges  Menschliches  Ei.  Arch.  f.  Anat.  u.  Physiol.,  Anat.  Abth., 
1890. 

KEIBEL,  F.:  Entwickelung  der  ausseren  Korperform  der  Wirbeltierembryonen.  In 
Hertwig's  Handbuch  der  vergleich.  u.  experiment.  Entwickelungslchre  der  Wirbeltiere.  Bd.  I, 
Teil  I,  1906. 

KEIBEL,  F.,  and  ELZE,  C.:  Normentafel  zur  Entwickelungsgeschichte  des  Menschen. 
Jena,  1008. 

KEIBEL,  F.,  and  MALL,  F.  P.:   Manual  of  Human  Embryology.     Vol.  I,  1910. 

KOLLMANN,  J. :  Die  Korperform  menschlicher  normaler  und  pathologischer  Embryonen. 
Arch.  f.  Anat.  u.  Physiol.,  Anat.  Abth.  Suppl.,  1889. 

KOLLMANN,  J.:  Handatlas  der  Entwickelungsgeschichte  des  Menschen.     Jena,  1907. 

LEOPOLD,  G.:  Ueber  ein  sehr  junges  menchliches  Ei.     Leipzig,  1906. 

MALL,  F.  P.:  A  Human  Embryo  Twenty-six  Days  Old.  Jour,  of  MorphoL,  Vol.  V, 
1891. 

MALL,  F.  P.:  A  Human  Embryo  of  the  Second  Week.     Anat.  Anz.,  Bd.  VIII,  1893. 

MALL,  F.  P.:  Human  Embryos.  Wood's  Reference  Handbook  0}  the  Medical  Sciences, 
Vol.  Ill,  1901. 

MEYER,  H.:  Die  Entwickelung  der  Urnieren  beim  Menschen.  Arch.  j.  mik.  Anat., 
Bd.  XXXVI,  1890. 

PETERS,  H.:  Ueber  die  Einbettung  des  menschlichen  Eies,  und  das  fruheste  bisher 
bekannte  menschliche  Placentarstadium.  Leipzig  und  Wien,  1899. 

RABL,  C.:  Die  Entstehung  des  Gesichtes.     I.  Heft.     Leipzig,  1902.     Folio. 

REICHERT,  B.:  Beschreibung  einer  fruhzeitigen  menschlichen  Frucht.  Abhandl. 
preuss.  Akad.,  Berlin,  1873. 


162 


TEXT-BOOK  OF  EMBRYOLOGY. 


SELENKA,  E.:  Studien  iiber  die  Entwickelungsgeschichte  der  Tiere;  (Menschenaffen). 
Wiesbaden,  1908.  Parts  8  to  10. 

VON  SPEE,  GRAF:  Beobachtungen  an  einer  menschlichen  Keimscheibe  mit  offener 
Medullarrinne  und  Canalis  neurentericus.  Arch.  /.  Anat.  u.  Physiol.,  Anat.  Abth.,  1889. 

VON  SPEE,  GRAF:  Ueber  friihe  Entwickelungsstufen  des  menschlichen  Eies.  Arch.  }. 
Anat.  u.  Physiol.,  Anat.  Abth.,  1896. 

STUBENRAUCH-  Inaug.     Dissert.     Miinchen,  1889. 

THOMPSON,  A.:  Contributions  to  the  History  of  the  Structure  of  the  Human  Ovum 
Before  the  Third  Week  after  Conception,  with  a  Description  of  Some  Early  Ova.  Edin- 
burgh Med.  andSurg.  Journal,  Vol.  Ill,  1839. 


PART  II. 


ORGANOGENESIS. 


CHAPTER  IX. 

THE  DEVELOPMENT  OF  THE  CONNECTIVE  TISSUES  AND  THE 

SKELETAL  SYSTEM. 

All  the  connective  or  supporting  tissues  of  the  body,  except  neuroglia, 
are  derived  from  the  mesoderm.  This  does  not  imply,  however,  that  all  the 
mesoderm  is  transformed  into  connective  tissues;  for  such  structures  as  the 
endothelium  of  the  blood  vessels  and  lymphatic  vessels,  probably  blood  itself, 
the  epithelium  lining  the  serous  cavities,  smooth  and  striated  muscle,  and  a  part 
of  the  epithelium  of  the  urogenital  system  are  derived  from  mesoderm. 


Primitive  groove 


Ectoderm 


Mesoderm 


Entoderm 


FlG.  138. — Transverse  section  of  chick  embryo  of  27  hours'  incubation.     Photograph. 

The  origin  of  the  mesoderm  itself  has  been  discussed  elsewhere  (p.  85). 
In  this  connection  it  is  sufficient  to  recall  that  it  is  situated  between  the  ectoderm 
and  entoderm  and  consists  of  several  layers  of  closely  packed  cells  (Fig.  138). 
The  axial  portion  in  the  neck  and  body  regions  becomes  differentiated  into  the 
primitive  segments.  At  the  same  time  a  cleft  (the  ccelom)  separates  the  more 
peripheral  portion  into  a  parietal  and  a  visceral  layer  (Figs.  139  and  141).  In 
the  head  region  where,  in  the  higher  animals,  there  is  little  or  no  indication  of 

165 


166 


TEXT-BOOK  OF  EMBRYOLOGY. 


Ectoderm 
I 


Neural 

tube 

i 


Primitive 
segment 


Ectoderm 


i 
Notochord 


Visceral 
Mesoderm 


I 
Coelom 


FIG.  139. — Transverse  section  of  chick  embryo  (2  days'  incubation).     Photograph. 
The   parietal   mesoderm   (lying  above   the  ccelom)    is   not   labeled.     The  two  large  vessels  under 
the  primitive  segments  are  the  primitive  aortae.     Spaces  separating  germ  layers  are  due  to 
shrinkage. 


Mesoderm 
(mesenchyme) 


Neural  tube 


Ectoderm 


Pharynx 


Entoderm 


FIG.  140. — Transverse  section  through  head  region  of  chick  embryo  of  42  hours' 
incubation.     Photograph. 


THE   CONNECTIVE  TISSUES   AND   THE   SKELETAL  SYSTEM. 


167 


segments  and  coelom,  the  mesoderm  simply  fills  in  the  space  between  the 
ectoderm  and  entoderm  (Fig.  140).  Portions  of  the  mesoderm  in  all  these 
regions  are  destined  to  give  rise  to  connective  tissues.  Each  primitive  segment 
soon  becomes  differentiated  into  three  parts — the  sderotome,  cutis  plate  and 
myotome  (Fig.  142).  Of  these,  only  the  sclerotome  and  cutis  plate  are  directly 
concerned  in  the  formation  of  connective  tissues,  the  myotomes  giving  rise  to 
striated  voluntary  muscle.  The  sclerotomes  are  destined  to  give  rise  to  the 


Neural  tube 


Intermediate.^ 
cell  mass  ~ 


Visceral  mesoderm 


Primitive  segment 


Intermediate 
cell  mass 


Mesothelium  "O 


*•"•?•  7"      Ectoderm 


1 ,   Parietal 

mesoderm 


Lateral 
body  wall 


Umbilical  vein 


FIG.  141. — Transverse  section  of  human  embryo  with  13  primitive  segments;  section  taken 
through  the  6th  segment.     Kollmann. 

vertebrae  and  other  forms  of  connective  tissue  in  their  neighborhood,  the  cutis 
plates  to  a  part,  at  least,  of  the  corium  of  the  skin.  The  parietal  and  visceral 
layers  of  the  mesoderm  (except  the  mesothelium  lining  the  ccelom)  and  the 
mesoderm  of  the  head  region  are  destined  to  give  rise  to  the  various  types  of 
connective  tissue  forming  parts  of  the  other  organs  of  the  body. 

HISTOGENESIS. 

The  sclerotomes  and  cutis  plates  at  first  constitute  parts  of  the  primitive 
segments,  and  are  composed  of  epithelial-like  cells  with  little  intercellular  sub- 
stance. The  intercellular  substance  gradually  increases  in  amount  so  that  the 


168 


TEXT-BOOK  OF  EMBRYOLOGY. 


Neural  crest 


Myotome  \ 


f  Cutis  plate 


i  Muscle  plate 
Scl.1 

Pronephros 


Parietal  mesoderm~- 
Intesti 


Myotome 


Sclerotome 


Visceral  mesoderm 


FIG.  142. — Transverse  section  of  human  embryo  of  the  3rd  week.     Scl.1,  Break  in  myotome  at 
point  where  sclerotome  is  closely  attached.     KoUmann. 


Neural  tube   — HP*! 


Intersegmental  . 
artery 


Intersegmental  - 
artery 


Ectoderm 


v          i   *t!t  -> 
tt»)*.«M»/4X« 

•3M& 

SSZL 


•/i""  Sclerotome 


~S5Ti«t  *• 

^?%v 

^g^i 

«**ii5^»-«- 
^*«s&  B*J.- 


>' — Myocoel 


FIG.  143. — Three  primitive  segments  from  sagittal  section  of  human  embryo  of 
the  3rd  week.     Kollmann. 


THE   CONNECTIVE   TISSUES   AND   THE   SKELETAL  SYSTEM.  169 

cells  become  more  widely  separated  from  one  another,  at  the  same  time  assum- 
ing oval  or  spindle  shapes  and  then  irregular  branching  forms  (Fig.  144). 
The  rest  of  the  mesoderm,  except  the  mesothelium,  also  undergoes  a  similar 
transformation  so  that  structurally  its  cells  are  indistinguishable  from  those 
derived  from  the  sclerotomes  and  cutis  plates. 

Thus  the  tissue  from  which  the  connective  tissues  in  general  are  derived  is 
composed  at  one  stage  of  irregular  branching  cells,  with  a  relatively  large 
amount  of  a  homogeneous  substance  filling  the  interstices  among  the  cells. 
The  question  of  the  relation  of  these  cells  to  one  another  has  not  been  settled 


m 


FIG.  144. — Mesenchymal  tissue  from  somatopleure  of  a  5  mm.  human  embryo. 
Mesothelium  is  shown  along  lower  border  of  figure. 

By  some  it  is  held  that  they  are  simply  individual  units,  structurally  independ- 
ent of  one  another.  By  others  it  is  maintained  that  the  branches  of  each 
cell  anastomose  with  branches  (5f  neighboring  cells,  to  form  a  syncytium,  and  that 
the  syncytial  character  is  retained  in  the  connective  tissue  derivatives  (Mall). 
That  intercellular  substance  is  derived  originally  from  the  cell  can  scarcely 
be  denied.  All  the  cells  of  the  organism  are  derived  from  the  fertilized  ovum. 
As  soon  as  two  or  more  cells  are  formed  by  segmentation  of  the  ovum,  they  are 
either  simply  in  apposition  or  else  they  are  united  by  something  in  the  nature  of 
a  "cement"  substance  which  must  have  been  derived  from  the  cells  themselves. 
In  the  connective  tissues  this  intercellular  ground  substance  is  a  prominent 


170 


TEXT-BOOK  OF  EMBRYOLOGY. 


feature,  and  while  it  may  increase  independently  of  the  cells  it  must  primarily 
have  a  cellular  origin. 

Fibrillar  Forms. — The  first  type  of  connective  tissue  to  be  derived  from 
the  embryonic  non-fibrillar  form  is  areolar  tissue.  Areolar  tissue  is  composed 
of  comparatively  few  cells  and  much  intercellular  substance,  the  latter  in  turn 


FIG.  145. — Fibril  forming  cells  from  fresh  subcutaneous  tissue  of  head  of  chick  embryo.     Boll. 

being  composed  of  fibers  and  "ground  substance."  The  fibers  are  of  two 
kinds,  "white"  or  fibrillated  and  "yellow"  or  elastic.  To  this  type  of  tissue 
in  the  embryo  the  term  embryonic  connective  tissue  has  been  applied. 

The  origin  of  the  fibers  is  an  unsettled  question.     Some  investigators  hold 
that  they  are  derived  from  the  homogeneous  "ground  substance"  by  a  process 


FIG.  146. — Connective  tissue  (mesenchymal)  cells  from  larval  salamander.     Flemming. 

of  differentiation  (Ranvier,  Merkel).  The  view  that  is  best  supported  by 
direct  observation,  however,  is  that  the  fibers  are  derived  from  the  cells 
(Boll,  Spuler,  Flemming).  The  cytoplasm  at  the  periphery  of  the  cells  and 
their  processes  becomes  differentiated  into  extremely  delicate  fibrillae  which 
become  grouped  into  bundles  (fibers)  and  then  become  separated  from  the 


THE   CONNECTIVE   TISSUES   AND   THE  SKELETAL  SYSTEM. 


171 


parent  cells  and  lie  free  in  the  "ground  substance"  (Figs.  145,  146).  This 
applies  to  both  fibrillated  and  elastic  fibers  and  the  same  cell  may  produce 
both  kinds  of  fibers,  i.  e.,  the  same  cell  that  produces  fibrillated  ("white")  fibers 
may  also  produce  elastic  ("yellow")  fibers.  The  fibers,  although  not  derived 
primarily  from  the  "ground  substance,"  probably  do  increase  in  size  by  intus- 
susceptive  growth.  Thus  the  "ground  substance,"  while  probably  not  capable 
of  producing  fibers,  is  an  active  factor  in  their  further  growth. 


FIG.  147. — Longitudinal  section  of  developing  ligament  from  finger  of 
human  foetus  of  6  months.     Photograph. 

In  any  type  of  connective  tissue  where  the  fibers  form  the  most  characteristic 
feature,  such  as  the  looser  forms  (areolar,  reticular)  or  such  as  the  denser  forms 
(fascia,  tendons,  ligaments),  the  structure  depends  upon  the  secondary  ar- 
rangement of  the  fibers  and  not  upon  any  peculiarity  of  origin.  In  areolar 
tissue,  for  example,  the  fibers  are  derived  from  the  cells,  as  described  above,  and 
become  so  arranged  as  to  look  haphazard.  In  fascia,  tendons  and  ligaments 
the  fibers  arise  in  the  same  manner  but  come  to  lie  parallel,  with  the  cells  en- 
closed among  them  in  more  or  less  distinct  rows  (Fig.  147). 

Adipose  Tissue. — Adipose  tissue  is  a  form  of  connective  tissue  in  which 
the  fatty  element  replaces  to  a  great  extent  the  cytoplasm  in  many  of  the 
embryonic  connective  tissue  cells.  It  always  develops  in  close  relation  to  blood 


172 


TEXT-BOOK  OF  EMBRYOLOGY. 


vessels,  and  first  appears  in  the  axilla  and  groin  about  the  thirteenth  week. 
It  is  formed  in  other  places  at  later  periods,  even  during  adult  life,  but  the 
mode  of  development  is  always  the  same.  In  some  of  the  cells  in  the  neigh- 
borhood of  small  blood  vessels  minute  droplets  of  fat  are  deposited.  The 
origin  of  the  fat  is  not  known.  The  droplets  become  larger,  other  smaller  ones 
appear,  and  finally  all  of  them  coalesce  to  form  a  single  large  drop  which  practi- 
cally fills  the  cell.  The  result  of  this  is  that  the  remaining  cytoplasm  is  pushed 
outward  and  forms  a  sort  of  pellicle  around  the  fat.  The  nucleus  also  is 
crowded  outward  and  comes  to  lie  flattened  in  the  pellicle  of  cytoplasm  (Fig. 


Small  artery 

FIG.  148. — Developing  fat  from  subcutaneous  tissue  of  pig  embryo  5  inches  long.  Small 
artery  breaking  up  into  capillary  network-  groups  of  fat  cells  developing  in 
embryonic  connective  tissue 

149) .  At  the  same  time  the  whole  fat  cell  increases  in  size  and  forms  a  relatively 
large  structure. 

Fat  cells  usually  develop  in  groups  or  masses  around  blood  vessels  (Fig. 
148).  The  neighboring  groups  gradually  enlarge  and  approach  each  other, 
but  do  not  fuse,  thus  leaving  more  or  less  fibrous  connective  tissue  between 
them,  which  constitutes  the  interlobular  tissue  seen  in  adult  adipose  tissue. 
Among  the  individual  cells  in  a  lobule  there  is  also  a  small  amount  of  fibrous 
tissue  present.  From  the  mode  of  development  a  small  artery  usually  affords 
the  blood  supply  for  each  lobule. 

Cartilage. — In  the  different  kinds  of  cartilage  the  matrix  probably  repre- 


THE   CONNECTIVE   TISSUES   AND   THE   SKELETAL  SYSTEM. 


173 


sents  a  modification  of  the  "ground  substance"  of  the  original  embryonic 
tissue.  The  fibers  in  the  matrix  are  probably  derived  from  the  cells  in  the 
same  manner  as  the  fibers  in  the  fibrillar  forms  of  connective  tissue  (Fig.  150). 
Osseous  Tissue. — Here  again  the  basis  for  development  is  embryonic 
connective  tissue,  although  in  one  type  of  development  cartilage  precedes  the 
bone.  Two  types  of  ossification  are  recognized — intramembranous  and  intra- 
cartilaginous  or  endochondral.  In  intramembranous  ossification  calcium  salts 
are  deposited  in  ordinary  embryonic  connective  tissue.  In  intracartilagi- 


Capillary 


Embryonic 
connective  tissue 


Arteriole 


FIG.  149. — Developing  fat  from  subcutaneous  tissue  of  pig  embryo  5  inches  long.  Fat  (stained 
black)  developing  in  embryonic  connective  tissue  cells.  At  the  right  are  five  individual  cells 
showing  stages  of  development  from  an  embryonic  cell  to  an  adult  fat  cell. 


nous  ossification  hyalin  cartilage  first  develops  in  the  same  general  shape  as 
the  future  bone  and  the  calcium  salts  are  afterward  deposited  within  the  mass  of 
cartilage.  It  is  customary  to  speak  also  of  another  type  of  ossification — sub- 
periosteal — in  which  the  calcium  salts  are  deposited  under  the  periosteum. 

INTRAMEMBRANOUS  OSSIFICATION. 

This  is  the  type  of  ossification  by  which  many  of  the  flat  bones  of  the  skull 
and  face  are  formed.  The  region  in  which  these  bones  are  to  develop  consists 
of  embryonic  connective  tissue.  At  certain  points  in  this  region  bundles  of 
connective  tissue  fibers  become  impregnated  with  calcium  salts.  Such  areas  are 
known  as  calcification  centers.  In  each  of  these  areas  the  cells  increase  in  num- 
ber, the  tissue  becomes  very  vascular  and  some  of  the  cells,  becoming  more  or 
less  round  or  oval,  with  distinct  nuclei  and  a  considerable  amount  of  cytoplasm, 


174 


TEXT-BOOK  OF  EMBRYOLOGY. 


Endoplasm  with 
"white"  fibers 


FIG.  150. — Connective  tissue  cells  from  intervertebral  disk  of  calf  embryo;  showing  origin  of 
"white"  and  elastic  fibers  in  protoplasm  of  cells.  Ectoplasm  represents  a  modified  part 
of  the  protoplasm.  Hansen. 


FIG.  151. — Vertical  section  through  frontal  bone  of  human  foetus  of  4  months. 
(Intramembranous  ossification.)     Photograph. 


THE   CONNECTIVE   TISSUES   AND   THE   SKELETAL  SYSTEM.  175 

arrange  themselves  in  single,  fairly  regular  rows  along  the  bundles  of  calcined 
fibers.  The  differentiated  cells  are  known  as  osteoblasts  (bone  formers) ,  and  the 
whole  tissue  is  now  known  as  osteo genetic  tissue.  Under  the  influence  of  the  osteo- 
blasts a  thin  layer  of  calcium  salts  is  deposited  between  the  osteoblasts  and  the 
calcined  fibers.  In  this  way  the  first  true  bone  is  formed,  and  the  calcification 
center  becomes  an  ossification  center.  Successive  layers  or  lamellae  of  calcium 
salts  are  laid  down  and  some  of  the  osteoblasts  become  enclosed  between  the 
lamella?  to  form  the  bone  cells  (Figs.  151  and  152).  The  spaces  in  which  the  bone 
cells  lie  are  the  lacuna.  At  the  same  time  the  fibers  also  are  enclosed  within  the 
bone  and  give  it  its  characteristic  fibrous  structure  (Fig.  152). 

Such  a  process  results  in  the  formation  of  irregular,  anastomosing  trabeculae 
of  bone.     The  spaces  among  the  trabeculae  are  known  as  primary  marrow 

Osteogenetis 

tissue  Osteoclast  Lacunae 


Bone 


Calcified  fibers  Osteoblasts 

FIG.  152. — From  vertical  section  through  parietal  bone  of  human  foetus  of  4  months. 
Bone  cells  not  shown  in  lacunae.     (Intramembranous  ossification.) 

spaces  and  contain  osteogenetic  tissue  (Fig.  151).  This  type  of  bone,  consisting 
of  irregular,  anastomosing  trabeculae  and  enclosed  marrow  spaces,  is  known  as 
spongy  bone.  The  spongy  bone  thus  formed  is  covered  on  its  outer  side  by  a 
layer  of  connective  tissue  which  from  its  position  is  called  the  periosteum 
(Fig.  151),  and  which  represents  a  part  of  the  original  embryonic  connective 
tissue  membrane  in  which  the  bone  was  laid  down.  During  its  development 
the  periosteum  becomes  an  exceedingly  dense  fibrous  membrane  which  is  closely 
applied  to  the  surface  of  the  bone. 

In  a  growing  embryo,  provision  must  be  made  for  increase  in  the  size  of  the 
cranial  cavity  to  accommodate  the  growing  brain.  This  is  accomplished  in 
the  following  manner :  On  the  inner  surface  of  the  newly  formed  bone,  large 
multinuclear  cells  appear,  which  are  known  as  osteoclasts  (bone  destroyers). 
The  osteoclasts  are  unusually  large  cells  with  a  large  number  of  nuclei  and 
abundant  cytoplasm,  and  in  sections  can  be  seen  lying  in  depressions  in  the 


176 


TEXT-BOOK  OF  EA1BRYOLOGY. 


bone — Howslip's  lacuna  (Fig.  152).  They  apparently  possess  the  power  of 
dissolving  bone  tissue.  While  the  destruction  of  bone  by  the  osteoclasts  is 
going  on  on  the  inner  surface,  new  bone  is  being  formed  on  the  outer  surface, 
especially  under  the  periosteum  where  the  osteoblasts  are  most  numerous. 
Thus  the  layer  of  bone  gradually  comes  to  lie  farther  and  farther  out  and  the 
cranial  cavity  is  enlarged.  So  long  as  the  cranial  cavity  continues  to  enlarge 


Cartilage 


Osteogenetic  tissue 


Intracartilaginous 
bone 


Periosteum 
(perichondrium) 


k  Ossification  center 


Calcification  zone 


FIG.  153. — Longitudinal  section  of  one  of  the  metatarsal  bones  of  a  sheep  embryo. 
(Intracartilaginous  ossification. ) 

the  new  bone  is  of  the  spongy  variety,  but  toward  the  end  of  development  the 
trabeculas  become  thicker  and  finally  come  together  to  form  the  compact  bone 
characteristic  of  the  roof  of  the  skull.  The  fact  that  the  new  bone  laid  down 
during  the  enlargement  of  the  cranial  cavity  is  laid  down  under  the  periosteum 
has  led  to  the  term  subperiosteal  ossification.  The  process  is  essentially  the 
same  as  in  the  original  intramembranous  ossification. 

INTRACARTILAGINOUS  OSSIFICATION. 

In  this  type  of  ossification  hyalin  cartilage  is  first  formed  in  a  shape  which 
corresponds  very  closely  to  the  shape  of  the  future  bone.  For  example,  the 
femur  is  first  represented  by  a  piece  of  hyalin  cartilage  which  develops  from 


THE   CONNECTIVE   TISSUES  AND   THE   SKELETAL  SYSTEM. 


177 


the  original  embryonic  connective  tissue.  On  the  surface  of  the  cartilage  a 
membrane  of  dense  fibrous  connective  tissue,  known  as  the  perichondrium, 
develops  (Fig.  153).  In  most  cases,  ossification  begins  about  the  middle 
of  the  piece  of  cartilage,  corresponding  to  the  middle  of  the  shaft  of  a  long 
bone  (Fig.  153).  The  cell  spaces  enlarge  and  in  some  cases  the  septa  of  matrix 
between  the  enlarged  spaces  break  down,  so  that  several  cells  may  lie  in  one 
space.  The  cell  spaces  radiate  from  a  common  center,  but  a  little  later  they 
come  to  lie  in  rows  parallel  with  the  long  axis  of  the  mass  of  cartilage.  During 
these  early  changes  lime  salts  are  deposited  in  the  matrix  of  the  cartilage  in 
this  region,  and  the  portion  so  involved  is  known  as  a  calcification  center. 

So  far  the  process  is  preparatory  to  actual  bone  formation.     Then  small 
blood  vessels  from  the  perichondrium  (periosteum)  grow  into   the  cartilage, 


Periosteal  bud 


Blood  vessel 


Cartilage  cells 


Cartilage  matrix 


Periosteum 
(Perichondrium) 


FIG.  154. — From  section  of  one  of  the  tarsal  bones  of  a  pig  embryo      Showing  periosteal  bud 
pushing  into  the  cartilage  at  the  ossification  center.     (Intracartilaginous  ossification.) 

carrying  with  them  some  of  the  embryonic  connective  tissue.  These  little 
ingrowths  of  connective  tissue  and  blood  vessels  are  known  as  periosteal  buds 
(Fig.  154).  The  septa  between  the  enlarged  cartilage  cell  spaces  break  down 
still  further,  forming  still  larger  spaces  into  which  the  periosteal  buds  grow. 
Many  of  the  connective  tissue  cells  are  transformed  into  osteoblasts — oval  or 
round  cells  with  distinct  nuclei  and  a  considerable  amount  of  cytoplasm — and 
with  the  fibers  and  blood  vessels  constitute  osteo genetic  tissue  (Fig.  155).  The 
cartilage  cells  in  this  region  disintegrate  and  disappear,  and  the  cavity  formed 
by  the  coalescence  of  the  cell  spaces  constitutes  the  primary  marrow  cavity  (Fig. 
155).  From  the  primary  marrow  cavity  osteogenetic  tissue  pushes  in  both 
directions  toward  the  ends  of  the  cartilage.  The  transverse  septa  between  the 
enlarged  cartilage  cell  spaces  break  down,  leaving  a  few  longitudinal  septa 
which  form  the  walls  of  long  anastomosing  channels  which  are  continuous  with 


178 


TEXT-BOOK  OF  EMBRYOLOGY. 


the  primary  marrow  cavity.  The  osteoblasts  arrange  themselves  in  rows  along 
the  septa  of  calcined  cartilage  and  a  thin  layer  or  lamella  of  calcium  salts  is 
deposited  between  them  and  the  cartilage.  Successive  lamellae  are  deposited 
in  the  same  manner  and  some  of  the  osteoblasts  become  enclosed  to  form  bone 
cells  (Fig.  156).  The  cartilage  in  the  center  gradually  disappears.  This 
region  where  bone  formation  is  going  on  is  known  as  an  ossification  center  (Fig. 
153)  and  the  irregular  anastomosing  trabecuke  of  bone  with  the  enclosed  marrow 
spaces  constitute  primary  spongy  bone. 

From  this  time  on,  ossification  gradually  progresses  toward  each  end  of  the 
cartilage,  and  at  the  same  time  a  special  modification  of  the  cartilage  precedes 
it.  Nearest  the  ossification  center  the  cartilage  cell  spaces  become  enlarged  and 

Cartilage  cell  spaces 
(primary  marrow  space) 


Disintegrating 
cartilage  cells 


Cartilage  cell 
spaces 


Blood  vessel » 


Osteogenetic  tissue  in 
primary  marrow  space 

FIG.  155. — From  same  section  as  Fig.  153;  showing  osteogenetic  tissue  pushing  into  the  cartilage 
and  breaking  it  up  into  trabeculae.     (Intracartilaginous  ossification.) 

arranged  in  rows  and  contain  cartilage  cells  in  various  stages  of  disintegration. 
Some  of  the  septa  break  down,  leaving  larger,  irregular  spaces;  the  remaining 
septa  become  calcified  (Fig.  153).  Passing  away  from  the  center  of  ossifica- 
tion, there  is  less  enlargement  of  the  cell  spaces  and  they  have  a  tendency  to  be 
arranged  in  rows  transverse  to  the  long  axis  of  the  cartilage;  there  is  also  a  lesser 
degree  of  calcification.  The  region  of  modified  cartilage  at  each  end  of  the 
ossification  center  passes  over  gradually  into  ordinary  hyalin  cartilage  and  is 
known  as  the  calcification  zone.  It  always  precedes  the  formation  of  bone  as 
the  latter  process  moves  toward  the  end  of  the  cartilage  (Fig.  153). 

Along  with  the  type  of  ossification  just  described  subperiosteal  ossification 
also  occurs  (Fig.  153).  Beneath  the  periosteum  (perichondrium)  is  a  layer  of 
connective  tissue  the  cells  of  which  are  transformed  into  osteoblasts.  They 


THE   CONNECTIVE  TISSUES   AND   THE   SKELETAL  SYSTEM. 


179 


deposit  layers  of  calcium  salts  on  the  surface  of  the  cartilage  in  the  same 
manner  as  around  the  trabeculae  inside  the  cartilage. 

The  transformation  of  the  spongy  bone  into  compact  bone  is  peculiar 
in  that  the  former  is  dissolved  and  then  replaced  by  new  bone.  This 
dissolution  is  brought  about  by  the  action  of  the  osteoclasts — large  mul- 
tinuclear  cells  the  origin  of  which  is  not  known.  By  the  process  of  dis- 
solution the  marrow  spaces  are  increased  in  size  and  are  known  as  Haver- 
sian  spaces.  Within  these  spaces  new  bone  is  then  deposited  layer  upon  layer, 
under  the  influence  of  the  osteoblasts,  until  the  Haversian  spaces  are  reduced 
to  narrow  channels,  the  Haversian  canals.  The  layers  of  bone  are  the  Haver- 
sian lamella.  The  interstitial  lamella  in  compact  bone  have  two  possible 
origins.  They  may  be  the  remnants  of  certain  lamellae  of  the  original  spongy 


Blood  vessel  Bone  Cartilage 


Bone  cell 


Cartilage  cell 


Cartilage  cell  space 


Osteogenetic  Osteoblasts 

tissue 

FIG.  156. — From  same  section  as  Fig.  153;  showing  bone  deposited  around  one  of  the 
trabeculae  of  cartilage.     (Intracartilaginous  ossification.) 

bone  which  were  not  removed  in  the  enlargement  of  the  primary  marrow  spaces, 
or  they  may  be  parts  of  early  formed  Haversian  lamellae  which  were  later  more 
or  less  replaced  by  other  Haversian  lamellae. 

The  fact  should  be  emphasized  that  although  it  is  convenient  to  describe 
three  types  of  bone  formation,  the  three  do  not  differ  essentially  from  one 
another.  The  similarity  of  intramembranous  and  subperiosteal  ossification  has 
already  been  noted  (p.  176).  In  both  these  types  the  bone  is  developed  within 
a  membrane  of  embryonic  connective  tissue  by  a  transformation  of  this  tissue 
into  osteogenetic  tissue  and  then  of  the  latter  into  bone.  The  only  way  in 
which  intracartilaginous  bone  formation  differs  from  the  other  two  types  is 
that  cartilage  is  first  formed  within  the  membrane  in  the  same  general  shape  as 
the  future  bone.  But  it  must  be  remembered  that  it  is  only  in  this  cartilage  that 
bone  is  developed  and  not  from  it,  the  bone  being  produced  by  osteogenetic 


180 


TEXT-BOOK  OF  EMBRYOLOGY. 


tissue  which  in  turn  is  derived  from  the  embryonic  connective  tissue  brought 
into  the  cartilage  by  the  periosteal  bud. 

GROWTH  OF  BONES. — The  way  in  which  the  cranial  cavity  enlarges  has  been 
described  on  page  175.  While  the  process  of  enlargement  is  going  on,  the 
individual  bones  increase  in  size  principally  by  the  addition  of  new  bone  along 
their  edges. 

Intracartilaginous  bones  grow  both  in  diameter  and  in  length.  It  has 
already  been  stated  that  the  primary  spongy  bone  formed  in  cartilage  is  dis- 
solved and  that  new  bone  is  deposited  under  the  periosteum.  This  naturally 
brings  about  an  enlargement  of  the  primary  marrow  cavity  and  at  the  same 
time  an  increase  in  the  diameter  of  the  bone  as  a  whole.  From  this  it  is  obvious 
that  the  compact  bone  of  the  shaft  of  a  long  bone  is  of  subperiosteal  origin,  the 
intracartilaginous  bone  having  been  completely  absorbed. 


1  B  ( 

FIG.  157. — Diagram  representing  growth  in  diameter  of  a  long  bone. 

from  Flourens. 


Modified 


The  fact  that  the  osseous  tissue  bordering  the  marrow  cavity  is  absorbed  and  that  new 
bone  is  deposited  under  the  periosteum  can  be  quite  clearly  demonstrated.  A  young 
growing  animal  is  fed  for  a  few  weeks  on  madder,  which  colors  all  the  bone  formed  during  that 
time  a  distinct  red.  If  the  animal  is  then  killed  and  sections  made  of  the  long  bones,  the 
outer  part  of  the  latter  will  appear  a  distinct  red.  Another  growing  animal  is  fed  on  madder 
for  a  few  weeks,  then  allowed  to  live  a  few  weeks  longer  without  madder.  Then  if  it  is 
killed  and  sections  made  of  the  bones,  the  red  bone  is  found  to  be  covered  with  a  layer  of 
uncolored  bone  which  was  deposited  after  the  madder  feeding  had  been  stopped.  If  a 
young  growing  animal  is  fed  on  madder  for  a  time  and  then  allowed  to  live  long  enough 
without  madder,  the  red  bone  will  be  found  lining  the  marrow  cavity.  (See  Fig.  157.) 

Growth  in  length  of  the  long  bones  takes  place  in  a  different  manner.  The 
primary  center  of  ossification  is  situated  near  the  middle  of  the  piece  of  cartilage, 
and  ossification  proceeds  in  both  directions  toward  the  ends  of  the  cartilage  to 
produce  the  diaphysis  or  shaft  of  the  bone.  In  each  end  of  the  cartilage  there 
appears  a  secondary  center  from  which  ossification  proceeds  in  all  directions  to 
produce  the  epiphysis.  Between  the  shaft  and  epiphysis  a  disk  of  cartilage 
remains,  and  here,  so  long  as  the  bone  is  growing,  new  cartilage  continues  to  be 
formed.  At  the  same  time  new  bone  is  being  formed  in  the  new  cartilage, 


THE   CONNECTIVE   TISSUES   AND   THE   SKELETAL  SYSTEM. 


181 


principally  in  the  part  next  the  shaft.  This  produces  an  elongation  of  the 
shaft,  the  two  epiphyses  being  carried  farther  and  farther  apart,  and  conse- 
quently a  lengthening  of  the  bone  as  a  whole.  When  the  bone  reaches  the 
required  length,  the  cartilage  disk  diminishes  and  finally  is  wholly  replaced  by 
bone,  being  represented  in  the  adult  only  by  the  epiphyseal  line.  (See  Fig.  158). 
MARROW. — The  forerunner  of  marrow  is  the  osteogenetic  tissue  in  the  pri- 
mary marrow  spaces,  which  in  turn  is  derived  from  embryonic  connective  tissue 
(Fig.  155).  During  the  development  of  bone,  great  numbers  of  osteoblasts  are 


FlG.  158. — Longitudinal  section  from  head  of  femur  of  young  dog.  Photograph. 
The  head  of  the  femur  is  shown  in  the  upper  part  of  the  figure,  the  end  of  the  shaft  in  the  lower 
part.  Between  the  two  the  lighter  line  represents  the  cartilage  between  the  primary  center 
of  ossification  (shaft)  and  the  secondary  center  (epiphysis,  head),  and  marks  the  site  of  the 
epiphyseal  line.  The  lighter  portion  covering  the  head  represents  the  cartilage  bordering 
the  joint  cavity. 


constantly  being  differentiated  from  the  connective  tissue  cells  and  many  of 
these  ultimately  become  bone  cells.  When  development  ceases,  osteoblasts 
cease  to  become  differentiated.  When  dissolution  of  bone  becomes  necessary, 
osteoclasts  appear.  Their  origin  is  not  known  with  certainty.  One  view  is 
that  they  are  derived  from  leucocytes,  another  is  that  they  are  derived  from  the 
endothelium  of  blood  vessels.  Their  relation  to  the  myeloplaxes  (giant  cells)  in 
adult  marrow  is  also  a  matter  of  doubt,  though  it  is  possible  that  the  two  forms 
are  identical.  Leucocytes  appear  in  the  marrow  at  an  early  stage,  but  whether 
they  arise  in  situ  or  are  brought  in  primarily  by  the  blood  vessels  is  not  known. 


182  TEXT-BOOK  OF  EMBRYOLOGY. 

There  is  also  just  as  much  uncertainty  in  regard  to  the  origin  of  red  blood  cells 
in  the  marrow.  At  an  early  stage  nucleated  red  cells  are  present,  and  from 
this  time  on,  the  marrow  affords  a  place  at  least  for  their  proliferation,  for  in 
the  adult  marrow  all  the  nucleated  forms  are  found,  as  well  as  the  non-nucleated. 
The  origin  of  the  marrow  cells  —  myelocytes  —  is  not  known.  The  fibrous 
part  of  the  osteogenetic  tissue  assumes  a  reticular  structure  and  forms  the 
reticulum  of  the  marrow.  In  young  marrow  there  is  little  or  no  fat  present,  but 
in  later  life  many  of  the  connective  tissue  cells  are  transformed  into  fat  cells 
(p.  172),  so  that  these  form  the  greater  part  of  the  marrow.  Such  a  process  oc- 
curs most  extensively  in  the  shaft  of  the  long  bones  and  gives  rise  to  "yellow" 
marrow.  In  the  heads  of  the  long  bones,  in  the  ribs,  and  in  the  short  bones  the 
marrow  retains  its  earlier  character  and  is  known  as  "red"  marrow. 

THE  DEVELOPMENT  OF  THE  SKELETAL  SYSTEM. 
The  Axial  Skeleton. 

The  Notochord.  —  The  notochord  (chorda  dorsalis)  constitutes  the 
primitive  axial  skeleton  of  all  Vertebrates,  yet  it  differs  from  the  other  skeletal 
elements  in  that  it  is  a  derivative  of  the  entoderm.  In  man  it  is  merely  a  tran- 
sient structure  and  disappears  early  in  fcetal  life,  leaving  but  a  slight  trace  of 
itself  in  the  intervertebral  disks.  In  embryos  of  2-3  mm.  the  cells  of  the 


Neural  —         _•  __  £  .«V  I'J  '«••-•* 

groove  '    .    r     -%---  '         /..V^--5'-^—  Ectoderm 

•^^HfrtasiM         -'i 

Mesoderm"          ~  -  .  --  -  •-  -•'  —  Mesoderm 


Anlage  of                        ^St3S^^^"^^^  ?£tt  **£>$£}&&*— 
nutoehiini -.^:.-£r—- • ?L^»V -Q^KP^SWhe*. "'. '         Entoderm 

FIG.  159. — From  transverse  section  of  human  embryo  with  8  pairs  of 
primitive  segments  (2.69  mm.).     Kollmann. 

entoderm  just  ventral  to  the  neural  groove  become  slightly  differentiated 
(Fig.  159)  and  then  form  a  groove  with  a  ventral  concavity.  The  groove  closes 
in,  becomes  constricted  from  the  parent  tissue  (entoderm)  and  lies  just  ventral  to 
the  neural  tube,  where  it  soon  becomes  surrounded  by  mesodermal  tissue.  This 
structure  is  the  notochord  and  constitutes  a  solid,  cylindrical  cord  of  cells 
extending  from  a  point  just  caudal  to  the  hypophysis  to  the  caudal  extremity  of 
the  embryonic  body.  In  embryos  of  17-20  mm.  the  mesodermal  tissue  around 
the  notochord  becomes  modified  to  form  the  chordal  sheath.  On  account  of  its 
position  the  notochord  naturally  becomes  embedded  in  the  developing  vertebral 


THE   CONNECTIVE   TISSUES  AND   THE   SKELETAL  SYSTEM. 


183 


column,  extending  through  the  bodies  of  the  vertebrae  and  the  intervertebral 
disks.  The  cells  are  at  first  of  an  epithelial  nature  (Fig.  159),  but  those  within 
the  vertebral  bodies  become  vacuolated  and  broken  up  into  irregular,  multinu- 
clear  masses  which  then  disappear.  The  cord  is  thus  first  interrupted  in  the 
vertebrae,  leaving  only  the  segments  within  the  intervertebral  disks.  Later  these 
segments  also  undergo  degenerative  changes,  but  persist  as  the  so-called  pulpy 
nuclei. 

While  the  notochord  is  morphologically  the  forerunner  of  the  axial  skeleton, 
and  persists  as  a  whole  in  Amphioxus,  and  in  part  in  Fishes  and  Amphibia,  in 
the  higher  forms  it  is  almost  exclusively  an  embryonic  structure  with  little  or  no 
functional  significance.  It  differs  in  origin  from  the  true  skeletal  elements  and 
becomes  involved  with  them  only  to  disappear  as  they  develop. 


Spinal  nerve 


Myotome 


Perichordal  sheath 
Cleft  between  two 
vertebral  anlagen 

Intersegmental 
artery 

•Notochord 


Parts  of  two 
adjacent  sclerotomes 


FIG.  160. — Five  myotomes  and  sclerotomes  from  sagittal  section  of  human  embryo  of  5  mm.  Bardeen. 

Each  sclerotome  is  differentiated  into  a  looser  cephalic  part  and  a  denser  caudal  part,  the  two 

being  separated  by  a  cleft  (fissure  of  von  Ebner). 

The  Vertebrae. — The  changes  which  occur  in  the  ventro-medial  parts  of  the 
primitive  segments  to  form  the  sclerotomes  have  already  been  described.  At 
the  same  time  it  was  stated  that  the  vertebrae,  with  the  other  types  of  connective 
tissue  around  them,  were  derived  from  the  mesenchymal  tissue  of  the  sclerotomes 
(p.  167;  see  also  Fig.  142).  The  segmentally  arranged  masses  forming  the 
sclerotomes  are  separated  by  looser  tissue  in  which  the  intersegmental  arteries 
develop.  The  arteries  mark  the  boundaries  between  the  sclerotomes  (Fig.  160). 
About  the  third  week  of  development  the  caudal  part  of  each  sclerotome  con- 
denses to  form  a  more  compact  mass  of  tissue,  and  a  little  later  becomes 
separated  from  the  cephalic  part  by  a  small  cleft  (Fig.  161).  From  the  denser 
caudal  part  a  secondary  mass  of  tissue  grows  medially  and  meets  and  fuses  with 
its  fellow  of  the  opposite  side,  thus  enclosing  the  notochord.  The  medial  mass 


184 


TEXT-BOOK  OF  EMBRYOLOGY. 


thus  formed  may  be  considered  as  the  anlage  of  the  body  of  a  vertebra.  Another 
secondary  mass  also  grows  dorsally  between  the  myotome  and  the  spinal  cord, 
forming  the  anlage  of  the  vertebral  arch.  A  third  mass  grows  ventro-laterally  to 
form  the  costal  process  (Figs.  162  and  163).  The  looser  tissue  of  the  cephalic 
part  of  each  sclerotome  also  sends  an  extension  medially  to  surround  the 
notochord,  and  fills  up  the  intervals  between  the  succeeding  denser  (caudal) 
parts.  The  looser  part  also  forms  a  sort  of  membrane  between  the  succeeding 
vertebral  arches.  The  tissue  between  the  denser  caudal  part  and  the  looser 
cephalic  part  of  each  sclerotome  is  destined  to  give  rise  to  an  intervertebral 
Jibrocartilage.  While  the  denser  tissue  forming  the  caudal  part  of  each  sclero- 


Dermis 


Myotome 


'Notochord 

Cleft 

Intersegmental  artery 

Perichordal  sheath 
Intervertebral  disk 
Interdiscal  membrane 


FIG.  161. — Six  myotomes  and  sclerotomes  from  sagittal  section  of  human  embryo  of  6  mm. 
Bardeen.     Compare  with  Fig.  160. 

tome  probably  gives  rise  to  the  greater  part  of  a  vertebra,  the  looser  tissue  of  the 
cephalic  part  is  also  involved  in  the  formation  of  the  cartilaginous  body,  as  will 
be  noted  again  in  the  following  paragraph.  The  peculiar  feature  of  the  process 
is  that  the  denser  caudal  part  of  a  sclerotome  becomes  associated  with  the  looser 
cephalic  part  of  the  next  succeeding  sclerotome,  so  that  each  vertebra  is  derived 
from  parts  of  two  adjacent  sclerotomes  and  not  from  a  single  sclerotome.  This 
naturally  brings  about  an  alternation  of  vertebrce  and  myotomes  (Fig.  161). 

So  far  the  anlagen  of  the  vertebrae  are  in  the  so-called  blastemal  stage. 

Following  the  blastemal  stage  and  beginning  in  human  embryos  of  about  15 
mm.,  comes  the  cartilaginous  stage  in  which  the  mesenchymal  anlagen  of  the 
vertebrae  are  converted  into  embryonic  hyalin  cartilage.  In  the  body  of  each 
vertebra  a  center  of  chondrification  appears  in  the  looser  tissue  of  the  caudal 


THE   CONNECTIVE  TISSUES   AND   THE   SKELETAL  SYSTEM. 


185 


part  and  gradually  enlarges  and  involves  the  denser  cephalic  part.  It  is  to  be 
noted  that  the  denser  tissue  of  the  cephalic  part  of  a  vertebral  body  corresponds 
to  the  caudal  part  of  a  sclerotome.  Two  chondrification  centers  appear,  one  on 


Costal  process 


Aorta 


Stomach 


Arch  of 
vertebra 


Notochord 


Body  of 
vertebra 


Mesonephros 


Liver 


FIG.  162. — Transverse  section  (dorsal  part)  of  pig  embryo  of  14  mm.     Photograph. 

each  side  of  the  medial  line,  but  the  two  soon  fuse  around  the  notochord  to 
form  a  single  center.  In  addition  to  the  center  in  the  body  of  the  vertebra,  one 
also  appears  in  each  half  of  the  vertebral  arch,  and  one  in  each  costal  process 

Arch  of 

vertebra        Interdorsal  membrane 


Notochord 


Costal  process 
FIG.  163. — Models  of  three  vertebrae  in  the  blastemal  stage;  from  an  embryo  of  n  mm.     Bardeen. 

(Fig.  164).  All  these  centers  then  enlarge  and  unite  to  form  a  single  mass  of 
cartilage  which  corresponds  quite  accurately  in  shape  to  the  future  bony 
vertebra.  Processes  then  grow  out  from  the  vertebral  arch.  These  represent 


186 


TEXT-BOOK  OF  EMBRYOLOGY. 


the  transverse  and  articular  processes  (Fig.  165).  Each  half  of  a  vertebral 
arch  meets  its  fellow  of  the  opposite  side  dorsal  to  the  spinal  cord,  and  from 
the  point  of  meeting  the  spinous  process  grows  out.  The  costal  processes  do 


Costal  process 
(rib) 


Body  of 

vertebra 


Costal  process 
(rib) 


Aorta 


Pleural  cavity  Liver  OEsophagus  Lung 

FIG.  164. — Transverse  section  (dorsal  part)  of  pig  embryo  of  35  mm.    Photograph. 

not  retain  their  connection  with  the  body  of  the  vertebra,  but  break  away 
and  become  the  rib  cartilages,  as  will  be  noted  again  in  connection  with  the 
development  of  the  ribs. 

Following  the  cartilaginous  stage  is  the  stage  of  ossification  in  which  the 

Arch  of  vertebra 
Post,  articular 
process 

Transverse  process 


Anterior  articular  process 

FIG.  165. — Models  of  the  6th,  yth  and  8th  thoracic  vertebrae  of  an  embryo  of  33  mm. 

(dorsal  view).     Bardeen. 
On  the  right  the  cartilage  is  shown,  on  the  left  the  surrounding  fibrous  tissue. 

vertebras  become  ossified  and  acquire  the  adult  condition.  Ossification  begins 
during  the  third  month  of  foetal  life  and  extends  over  a  long  period,  even  up  to 
the  age  of  twenty-five  years.  A  single  center  of  ossification  appears  in  the  body 


THE   CONNECTIVE   TISSUES  AND   THE  SKELETAL  SYSTEM. 


187 


of  each  vertebra,  and  following  this  a  center  in  each  half  of  the  vertebral  arch 
(Fig.  1 66).  Osseous  tissue  then  gradually  replaces  the  cartilage.  The  two 
halves  of  an  arch  fuse  dorsal  to  the  spinal  cord  during  the  first  year  of  post- 
natal life,  thus  completing  the  bony  arch.  The  arch  fuses  with  the  body  of  the 


•  Spinous  process 


—  Articular  process 


--»   *-^^L  -*s-^v  -V JLXI  ij 

^                              — Transverse  process 
'Lat.  ossif.  center 

Med.  ossif.  cents 

FIG.  166. — Thoracic  vertebra  and  ribs  of  human  embryo  of  55  mm.  (middle  of 

3rd  month).     Kollmann's  A  Has. 
Cartilage  indicated  by  stippled  areas,  ossification  centers  by  irregular  black  lines. 

vertebra  between  the  third  and  eighth  years.  Thus  it  is  seen  that  the  process  of 
ossification  is  a  slow  one,  and  this  is  even  more  striking  when  one  considers  the 
formation  of  the  secondary  centers.  For  at  about  the  age  of  puberty  a  secondary 
center  appears  in  each  of  the  cartilages  that  cover  the  ends  of  the  vertebrae,  pro- 

Spinous  process 
Transverse  process 
Articular  process 


Body  of  vertebra 


Upper  epiphyseal 
plate 


FIG.  167. — Lumbar  vertebra  (lateral  view)  showing  secondary  centers  of  ossification.     Sappey. 


ducing  disks  of  bone — the  epiphyses.  A  secondary  center  also  appears  in  the 
cartilage  on  the  tip  of  each  spinous  process  and  transverse  process,  and  in  the 
lumbar  vertebrae  one  appears  also  on  the  tip  of  each  articular  process  (Fig.  167). 
The  epiphyses  unite  with  the  vertebrae  any  time  between  sixteen  and  twenty- 


188 


TEXT-BOOK  OF  EMBRYOLOGY. 


five  years.  About  the  twenty-fifth  year  the  sacral  vertebrae  unite  to  form  a 
single  mass  of  bone,  and  a  similar  union  also  takes  place  between  the  more  or 
less  rudimentary  coccygeal  vertebrae. 

While  the  general  plan  of  development  is  practically  the  same  in  all  the 
vertebras,  there  are  a  few  noteworthy  modifications.  The  greatest  modification 
is  in  the  atlas  and  epistropheus  (axis).  The  entire  atlas  is  formed  from  the 
denser  caudal  part  of  a  sclerotome.  The  lateral  mass  and  the  posterior  (dorsal) 
arch  represent  the  vertebral  arch.  The  anterior  (ventral)  arch  represents  the 
hypochordal  bar,  a  plate  of  cartilage  which  develops  in  all  vertebrae  ventral  to 
the  notochord  but  disappears  in  all  except  the  atlas.  A  body  also  develops 
but  instead  of  forming  part  of  the  atlas  it  unites  with  the  body  of  the  epistro- 
pheus to  form  the  dens  (odontoid  process)  of  the  latter. 


Clavicle 


Suprasternal  cartilage 


Sternal  bar 


7th  rib 


FIG.  168. — Ventral  view  of  developing  sternum  of  human  embryo  of  30  mm. 
(beginning  of  3rd  month).     Rugc,  Kollmann's  Atlas. 

The  various  ligaments  of  the  vertebral  column  are  derived  from  the  embry- 
onic connective  tissue  surrounding  the  vertebrae.  The  embryonic  connective 
tissue  in  the  clefts  separating  the  developing  vertebrae  is  transformed  into  the 
intervertebral  fibrocartilages. 

The  Ribs. — It  has  been  stated  in  a  previous  paragraph  that  the  costal  proc- 
esses arise  as  outgrowths  from  the  denser  caudal  parts  of  the  sclerotomes;  that 
they  grow  in  a  ventro-lateral  direction  and  consequently  are  at  first  connected 
with  and  are  parts  of  the  bodies  of  the  vertebrae  (Figs.  162  and  165).  These 
costal  processes  are  the  anlagen  of  the  ribs,  and  they  continue  to  grow  ventrally 
until  they  practically  encircle  the  body,  the  ventral  ends  of  a  number  of  them 
fusing  in  the  medial  line  to  form  the  sternum.  The  primary  junctions  between 
the  costal  processes  and  vertebrae  are  dissolved,  and  the  embryonic  connective 
tissue  in  this  region  gives  rise  to  the  costo-vertebral  ligaments.  The  dissolu- 
tion of  the  junctions  leaves  the  ribs  simply  articulating  with  the  vertebrae. 


THE   CONNECTIVE  TISSUES  AND   THE   SKELETAL  SYSTEM. 


189 


A  chondrification  center  appears  in  each  costal  process,  shortly  after  that  in 
the  body  of  the  vertebra,  and  from  this  point  the  formation  of  cartilage 
gradually  extends  throughout  the  entire  rib. 

Ossification  begins  during  the  third  month  at  a  center  which  is  situated  near 
the  angle  of  the  rib  (Fig.  166).  At  the  age  of  eight  to  fourteen  years  a  second- 
ary center  appears  in  each  capitulum  and  iuberculum,  and  subsequently  fuses 
with  the  rest  of  the  rib  at  the  age  of  fourteen  to  twenty-five  years.  As  the 
tuberculum  develops,  the  transverse  process  of  the  corresponding  vertebra 
grows  ventrally  and  caudally  to  meet  it  and  form  the  articulation. 

The  ribs  reach  the  highest  degree  of  development  in  the  thoracic  region 
where  one  develops  on  each  side,  corresponding  to  each  vertebra.  The  first 
seven  or  eight  thoracic  ribs  extend  almost  to  the  mid- 
ventral  line  and  are  attached  to  the  sternum;  the  last  four 
or  five  become  successively  shorter  and  are  only  indirectly 
or  not  at  all  attached  to  the  sternum.  In  the  cervical 
region  the  ribs  do  not  reach  a  high  degree  of  development. 
Their  tips  simply  fuse  with  the  transverse  processes  of  the 
vertebrae  and  their  heads  with  the  bodies  of  the  vertebras, 
leaving  a  space — the  foramen  transversarium — through 
which  the  vertebral  vessels  pass.  The  seventh  cervical  rib 
may,  however,  reach  a  fairly  high  degree  of  development. 
In  the  lumbar  region  also  the  ribs  are  reduced  to  small 
pieces  of  bone  which  are  firmly  united  with  the  transverse 
processes  and  form  the  accessory  processes.  In  the  sacral 
region  the  rudimentary  ribs  unite  to  form  the  lateral  part 
(pars  later  alls}  of  the  sacral  bone.  After  the  blastemal 
stage  there  are  no  indications  of  ribs  in  the  coccygeal  region. 
In  the  blastemal  stage,  however,  there  is  a  small  bit  of  tissue  FIG.  169.— Sternum  of 
which  probably  represents  the  anlage  of  a  rib,  but  soon  showing  centers'  of 
fuses  with  the  transverse  process. 

The  Sternum. — The  sternum  is  formed  by  the  fusion 
of  the  ventral  ends  of  the  first  eight  or  nine  thoracic  ribs. 
A  longitudinal  bar  is  first  formed  on  each  side  of  the  medial 
line  by  the  fusion  of  the  ventral  ends  of  the  ribs  on  each  side;  then  the  two  bars 
unite  in  the  medial  line  to  form  a  single  piece  of  cartilage  (Figs.  168  and  169). 
Subsequently  the  last  one  or  two  ribs  become  separated  from  the  sternum, 
leaving  only  seven  or  eight  connected  with  it.  At  the  cephalic  end  of  the 
sternum  two  separate  pieces  of  cartilage — episternal  cartilages — appear,  with 
which  the  clavicles  articulate  (Fig.  168).  These  usually  unite  with  the  longi- 
tudinal bar  to  form  a  part  of  the  manubrium,  but  they  may  remain  separate 
and  ossify  to  form  the  suprasternal  bones  (ossa  suprasternalia). 


ossification.  Seven 
ribs  are  attached  on 
the  right  side,  8  on 
the  left.  Markmvski, 
Kollmann's  Atlas. 


190 


TEXT-BOOK  OF  EMBRYOLOGY. 


Ossification  begins  in  the  sternum  about  the  end  of  the  fifth  month  of  foetal 
life.  In  each  of  the  two  cephalic  segments  a  single  center  appears;  caudal  to  the 
second  segment  a  series  of  paired  centers  appears,  and  later  the  centers  of  each 
pair  fuse  into  a  single  center  (Fig.  169).  The  paired  centers  possibly  represent 
epiphyses  of  the  ribs.  Sometimes,  however,  the  centers  appear  as  a  single 
series,  that  is,  with  no  indication  of  a  paired  character.  The  ossification 
of  the  most  cephalic  segment,  along  with  the  episternal  cartilages,  produces  the 
manubrium  sterni.  Ossification  of  the  following  six  or  seven  segments  and  their 
union  produce  the  corpus  sterni.  The  bars  formed  from  the  most  caudal  ribs 
(excluding  the  false  ribs)  form  the  xyphoid  process.  This  process  remains  car- 


Olfactory  organ 
Hypophysis 
Visual  organ 

Prechordal  plate 

Auditory  organ 

Parachordal  plate 

Notochord 


Nasal  septum 

Olfactory  organ 
Hypophysis 
Visual  organ 

Prechordal  plate 
Auditory  organ 


Basal  (parachordal) 
plate 

Notochord 


FIG.  170. 


FIG.  171. 


FIG.  170. — Diagram  of  first  stage  in  the  development  of  the  cartilaginous 

primordial  cranium.     Wiedershcim. 
FIG.  171. — Diagram  of  later  stage  of  same.     Wiedersheim. 

tilaginous  for  a  long  period,  and  may  be  single,  perforated,  or  bifurcated,  de- 
pending upon  the  degree  of  fusion  between  the  two  primary  bars. 

The  Head  Skeleton. — Topographically  the  skeleton  of  the  head  appears 
as  the  cephalic  part  of  the  axial  skeleton.  Structurally  it  is  decidedly  different, 
for  it  is  adapted  to  different  conditions.  The  neural  tube  here  becomes  differ- 
entiated into  the  brain  with  its  many  and  dissimilar  parts.  In  connection  with 
the  brain  the  complicated  sense  organs  (nose,  eye  and  ear)  arise.  A  part  of 
the  alimentary  tract  and  portions  of  the  visceral  arches  are  also  inclosed 
within  the  head.  The  head  skeleton  is  specially  modified  to  accommodate 
these  highly  developed  organs,  and  becomes  extremely  complicated.  In 
general  the  skeleton  in  any  part  of  the  body  adapts  itself  to  the  other  structures 
and  not  the  other  structures  to  the  skeleton. 

The  anlage  of  the  skull  is  a  mass  of  embryonic  connective  tissue  which  sur- 


THE  CONNECTIVE  TISSUES  AND  THE  SKELETAL  SYSTEM. 


191 


rounds  the  cephalic  end  of  the  notochord,  extends  from  there  into  the  nasal 
region  and  also  extends  around  the  sides  and  dorsal  part  of  the  neural  tube 
(brain).  Unlike  the  anlage  of  the  vertebral  column,  the  anlage  of  the  skull 
shows  no  distinct  division  into  primitive  segments.  The  only  indications  of  a 
segmental  character  are  referred  to  in  a  succeeding  paragraph  (small  print, 

P-  193)- 

The  next  step  in  the  development  of  the  skull  is  the  appearance  of  cartilage 
in  certain  regions  of  the  embryonic  connective  tissue.  On  account  of  the  com- 
plicated arrangement  of  the  cartilage  in  the  human  skull,  it  is  best  to  consider 


Palatoquadrate 

Palatoquadrate 
Meckel's  cartilage 


Palatoquadrate 
Hypophysis 


Nasal  fossa 
Preorbital  process 


Roof  of  skull 
-  Marginal  bar 


Prechprdal  plate 
Prootic  incisure 
Jugular  foramen 


Notochord 
Otic  (auditory)  capsule 

Synotic  tectum 


FIG.  172. — Primordial  cranium  of  Salmo  salar  (salmon)  embryo  of  25  mm.     Dorsal  view.     Gaupp. 
Compare  with  Fig.  171  and  note  further  elaboration  of  parts  surrounding  the  sense  organs. 

first  its  more  simple  arrangement  in  the  lower  Vertebrates.  In  these  there  ap- 
pear in  the  embryonic  connective  tissue  around  the  cephalic  end  of  the  notochord 
two  bilaterally  symmetrical  pieces  of  cartilage,  which  extend  as  far  as  the 
hypophysis.  Then  two  other  bilaterally  symmetrical  pieces  appear,  extending 
from  the  hypophysis  to  the  nasal  region.  Subsequently  all  these  pieces  fuse 
into  a  single  mass  which  extends  from  the  cephalic  end  of  the  vertebral  column 
to  the  tip  of  the  nose,  enclosing  the  end  of  the  notochord  and,  to  a  certain  ex- 
tent, the  ear,  eye  and  olfactory  apparatus.  There  is  left,  however,  an  opening 
for  the  hypophysis.  From  this  mass  of  cartilage,  chondrification  extends  into 
the  embryonic  connective  tissue  along  the  sides  and  roof  of  the  cranial 


192 


TEXT-BOOK  OF  EMBRYOLOGY. 


cavity,  so  that  the  brain  and  sense  organs  are  practically  enclosed.  To  this 
capsule  the  term  cartilaginous  primordial  cranium  has  been  applied.  (See 
Figs.  170,  171,  172.) 

In  the  higher  Vertebrates,  chondrification  is  limited  to  the  basal  region  of  the 
skull,  while  the  side  walls  and  roof  are  formed  later  by  intramembranous  bone. 


Crista  galli 

~  Lamina  cribrosa 

Ala  magna  (sphenoid) 
Optic  foramen 

Ala  parva  (sphenoid) 


Meckel's  cartilage 
Malleus 

Incus 


Int.  acoustic  pore 
Jugular  foramen       - . 

Subarcuate  fossa 


Sella  turcica 
Dorsum  sellae 


Foramina 
(VII  Nerve) 

_    Auditory 
capsule 


Foramen 


Foramen  (XII  Nerve) 


Large  occipital  foramen  Occipital 

(foramen  magnum)        (synotic  tectum) 

FIG.  173. — Dorsal  view  of  primordial  cranium  of  human  embryo  of  80  mm. 

(3rd  month).     Gaupp.  Hertwig. 

The  membrane  bones  of  the  roof  of  the  skull  have  been  removed.     Through  the  large  occipital 
foramen  can  be  seen  the  first  three  cervical  vertebrae. 


In  the  human  embryo  chondrification  occurs  first  in  the  occipital  and  sphenoidal 
regions,  and  then  gradually  extends  into  the  nasal  (ethmoidal)  region.  A  little 
later  it  spreads  somewhat  dorsally  in  the  occipital  and  sphenoidal  regions  to  form 
part  of  the  squamous  portion  of  the  occipital  and  the  wings  of  the  sphenoid.  At 
the  same  time  cartilage  develops  in  the  embryonic  connective  tissue  surround- 


THE   CONNECTIVE  TISSUES  AND   THE   SKELETAL  SYSTEM. 


193 


ing  the  internal  ear  to  form  the  periotic  capsule  which  subsequently  unites  with 
the  occipital  and  sphenoidal  cartilages.  The  pieces  of  cartilage  thus  formed  con- 
stitute the  chondrocranium. 

In  connection  with  the  development  of  the  caudal  part  of  the  occipital  cartilage  there  is 
an  interesting  feature  which  is  at  least  indicative  of  a  segmental  character.  In  some  of  the 
lower  Mammals  there  are  four  fairly  distinct  condensations  of  embryonic  connective  tissue 
just  cranial  to  the  first  cervical  vertebra,  corresponding  to  the  first  cervical  nerve  and  the 
three  roots  of  the  hypo  glossal.  These  condensations  bear  a  general  resemblance  to  the 
primitive  segments  and  indicate  the  existence  of  four  vertebrae  which  are  later  taken  up  into 
the  chondrocranium.  In  the  human  embryo  the  condensations  are  less  distinct,  but  the 
existence  of  a  first  cervical  and  a  three-rooted  hypoglossal  nerve  in  this  region  suggests  an 
original  segmental  character.  If  this  is  true,  then  the  base  of  the  human  skull  is  formed 
from  the  unsegmented  chondrocranium  plus  four  vertebrae  which  become  incorporated  in 
the  occipital  region. 


Optic  foramen 


Ala  magna  (sphenoid) 

Ala  parva  (sphenoid) 


Nasal  capsule 
Nasal  septum 

Maxilla 


Vomer 
Palate  bone 


Mandible 

Meckel's  cartilage 

Cricoid  cartilage 


\  Styloid  process 

\     Cochlear  fenestra 
Malleus    \ 

Foramen  (XII  Nerve) 


Thyreoid  cartilage 


FIG.  174. — Lateral  view  of  primordial  cranium  of  human  embryo  of  So  mm. 

(3rd  month).     Gaupp,  Hertwig. 

The  membrane  bones  of  the  roof  of  the  skull  have  been  removed.     Compare  with  FIG.  173.     The 
maxilla,  vomer,  palate,  and  mandible  are  membrane  bones. 


In  addition  to  the  chondrocranium,  other  cartilaginous  elements  enter  into 
the  formation  of  the  skull,  all  of  which  are  derived  from  the  visceral  arches. 
Not  all  the  arches,  however,  produce  cartilage;  for  in  the  maxillary  process  of 
the  first  arch,  which  forms  the  upper  boundary  of  the  mouth,  cartilage  does  not 
appear,  and  the  bones  which  later  develop  in  it  are  of  the  membranous  type. 
The  mandibular  process  of  the  first  arch  produces  a  rod  of  cartilage — Meckel's 
cartilage.  This  gives  rise,  at  its  proximal  end,  to  a  part  of  the  auditory  ossicles, 
but  the  cartilage  in  the  jaw  proper  soon  wholly  or  almost  wholly  disappears. 
The  cartilage  of  the  second  arch  becomes  connected  with  the  skull  in  the  region 


194 


TEXT-BOOK  OF  EMBRYOLOGY. 


of  the  periotic  capsule.     The   cartilages  of  the  other  three  arches  are  only 
indirectly  connected  with  the  skull  and  will  be  considered  later. 

Figs.  1 73  and  174  show  the  condition  of  the  chondrocranium  in  a  human 
embryo  of  80  mm.  (third  month) .  Although  at  first  glance  it  seems  exceedingly 
complicated,  a  careful  study  and  comparison  of  the  various  parts  will  aid  the 
student  in  his  comprehension  of  the  cartilaginous  foundation  upon  which  the 
skull  is  built. 

OSSIFICATION  OF  THE  CHONDROCRANIUM. 

In  the  human  foetus  ossification  begins  in  the  occipital  region  during  the 
third  month.  Four  centers  appear  which  correspond  to  the  four  parts  of  the 
adult  occipital  bone  (Fig.  175).  (i)  An  unpaired  center  situated  ventral  to  the 
foramen  magnum.  From  this  center  ossification  proceeds  in  all  directions  to 


Interparietal 
(of  lower  forms) 


Squamous  part 
(intramemb.) 


Squamous) 
part      I 


Kerkringius'  bone 


Squamous  part 
(intracartilag.) 


•Lateral  part 


Basilar  part 


FIG.  175.— Occipital  bone  of  human  embryo  of  21.5  cm.     Kollmann's  Atlas. 


form  the  pars  basilaris  (basioccipital).  (2  and  3)  Two  lateral  centers,  one 
on  each  side.  From  these,  ossification  proceeds  to  produce  the  paries  laterales 
(exoccipital)  which  bear  the  condyles.  (4)  A  center  dorsal  to  the  foramen 
magnum.  This  produces  the  pars  squamosa  (supraoccipital)  as  far  as  the  supe- 
rior nuchal  line.  Beyond  this  line  the  pars  squamosa  is  of  intramembranous 
origin.  (See  p.  196.)  At  birth  the  four  parts  are  still  separated  by  plates  of 
cartilage.  During  the  first  or  second  year  after  birth  the  partes  laterales 
unite  with  the  pars  squamosa,  and  about  the  seventh  year  the  pars  basilaris 
unites  with  the  rest  of  the  bone. 


THE   CONNECTIVE   TISSUES   AND   THE   SKELETAL  SYSTEM.  195 

In  the  sphenoidal  region  ossification  begins  at  a  number  of  centers  which, 
as  in  the  occipital  region,  correspond  generally  to  the  parts  of  the  adult  sphenoid 
bone  (Fig.  176).  (i  and  2)  About  the  ninth  week  an  ossification  center 
appears  on  each  side  in  the  cartilage  which  corresponds  to  the  ala  magna 
(alisphenoid).  (3  and  4)  About  the  twelfth  week  a  center  appears  on  each 
side  which  corresponds  to  the  ala  parva  (orbitosphenoid).  (5  and  6)  A 
short  time  after  this  a  center  appears  on  each  side  of  the  medial  line  in  the 
basal  part  of  the  cartilage,  and  the  two  centers  subsequently  fuse  to  produce  the 
corpus  (basisphenoid).  (7  and  8)  Lateral  to  each  basal  center,  another  center 
appears  which  represents  the  beginning  of  the  lingula.  (9  and  10)  Finally 
two  centers  appear  in  the  basal  part  of  the  cartilage,  in  front  of  the  other 
basal  centers,  and  then  fuse  to  form  the  presphenoid.  As  in  the  case  of  the  oc- 
cipital bone,  not  all  of  the  adult  sphenoid  is  of  intracartilaginous  origin;  for  the 

Ala  parva  ••• 

Ala  magna 


Lingula 


Corpus 
(basisphenoid) 

FIG.  176. — Sphenoid  bone  of  embryo  of  3^-4  months.     Sappey. 
The  parts  that  are  still  cartilaginous  are  represented  in  black. 

upper  anterior  angle  of  each  ala  magna  is  of  intramembranous  origin,  as  are  alsa 
the  medial  and  lateral  laminae  of  the  pterygoid  process.  The  pterygoid  hamuluSy. 
however,  is  formed  by  the  ossification  of  a  small  piece  of  cartilage  which  de- 
velops on  the  tip  of  the  medial  lamina.  The  fusion  of  these  various  parts  oc- 
curs at  different  times.  The  lateral  pterygoid  lamina  unites  with  the  alisphe- 
noid before  the  sixth  month  of  fcetal  life;  about  the  sixth  month  the  lingula  fuses 
with  the  basisphenoid,  and  the  presphenoid  with  the  orbitosphenoid.  The 
alisphenoid  and  medial  pterygoid  lamina  fuse  with  the  rest  of  the  bone  during 
the  first  year  after  birth.  The  union  of  the  basisphenoid  and  basioccipital 
usually  occurs  when  the  growth  of  the  individual  ceases,  though  the  two  bones 
may  remain  separate  throughout  life. 

In  the  region  of  the  periotic  capsule,  several  centers  of  ossification  appear  in 
the  cartilage  during  the  fifth  month.  During  the  sixth  month  these  centers 
unite  to  form  a  single  center  which  then  gradually  increases  to  form  the  pars 
petrosa  and  pars  mastoidea  of  the  adult  temporal  bone.  The  mastoid  process  is 


196  TEXT-BOOK  OF  EMBRYOLOGY. 

formed  after  birth  by  an  evagination  from  the  pars  petrosa,  and  is  lined  by  an 
evaginated  portion  of  the  mucosa  of  the  middle  ear.  The  other  parts  of  the 
temporal  bone  are  of  intramembranous  origin,  except  the  styloid  process  which 
represents  the  proximal  end  of  the  second  branchial  arch. 

In  the  ethmoidal  region,  conditions  become  more  complicated  on  account  of 
the  peculiarities  of  the  nasal  cavities,  and  on  account  of  the  fact  that  the  cartilage 
is  never  entirely  replaced  by  bone,  and  that  "membrane"  bones  also  enter  into 
more  intimate  relations  with  the  "cartilage"  bones.  The  ethmoidal  cartilage 
at  first  consists  of  a  medial  mass,  which  extends  from  the  presphenoid  region  to 
the  end  of  the  nasal  process,  and  of  a  lateral  mass  on  each  side,  which  is  situated 
lateral  to  the  nasal  pit  (Fig.  174).  Ossification  in  the  lateral  mass  on  each  side 
produces  the  ethmoidal  labyrinth  (lateral  mass  of  ethmoid).  It  is  perhaps  not 
quite  correct  to  say  that  ossification  produces  the  ethmoidal  labyrinth,  for  at 
first  there  is  only  a  mass  of  spongy  bone  with  no  indication  of  the  honey-combed 
structure  characteristic  of  the  adult.  The  latter  condition  is  produced  by  a 
certain  amount  of  dissolution  of  the  bone  and  the  growth  of  the  nasal  mucosa 
into  the  cavities  so  formed.  By  the  same  process  of  dissolution  and  ingrowth  of 
nasal  mucosa  the  superior,  middle  and  inferior  concha  (turbinated  bones)  are 
formed.  The  medial  mass  of  cartilage  begins  to  ossify  after  birth  and  then  only 
in  its  upper  (superior)  edge.  It  forms  the  lamina  perpendicular  is  and  crista 
galli  and  extends  into  the  nose  as  the  nasal  septum.  The  lower  (inferior)  edge 
remains  as  cartilage  until  the  vomer,  which  is  a  membrane  bone  (p.  198), 
develops,  after  which  it  is  partly  dissolved.  The  lamina  cribrosa  (cribriform 
plate)  is  formed  by  bony  trabeculae  \vhich  extend  across  between  the  medial 
mass  and  the  lateral  masses  and  surround  the  bundles  of  fibers  of  the  olfactory 
nerve. 

MEMBRANE  BONES  OF  THE  SKULL. 

Under  this  head  we  shall  consider  only  those  bones  which  develop  apart 
from  the  visceral  arches,  those  which  involve  the  arches  being  considered  later. 
It  has  been  seen  that  by  far  the  greater  parts  of  the  bones  forming  the  base  of  the 
skull  are  of  intracartilaginous  origin.  On  the  other  hand,  those  forming  the 
sides  and  roof  of  the  skull  are  largely  of  intramembranous  origin.  In  the  case 
of  the  occipital  bone,  two  centers  of  ossification  appear  in  the  membrane  dorsal 
to  the  supraoccipital,  and  the  bone  so  formed  begins  to  unite  with  the  supra- 
occipital  during  the  third  month  of  foetal  life.  At  birth  the  union  is  usually 
complete,  though  for  a  time  an  open  suture  may  persist  on  each  side.  The  bone 
derived  from  the  two  centers  forms  that  part  of  the  occipital  squama  which  is 
situated  above  the  superior  nuchal  line;  the  part  below  the  line  is  of  intracarti- 
laginous origin  (p.  194).  The  adult  occipital  is  thus  a  composite  bone,  partly 
of  intramembranous,  partly  of  intracartilaginous  origin. 


THE   CONNECTIVE   TISSUES   AND   THE   SKELETAL  SYSTEM. 


197 


The  temporal  is  also  a  composite  bone,  the  petrous  and  mastoid  parts 
and  the  styloid  process  being  of  intracartilaginous  origin,  while  the  temporal 
squama  and  the  tympanic  part  are  of  intramembranous  origin.  During  the 
eighth  week  of  fcetal  life  a  center  of  ossification  appears  in  the  membrane  in  the 
temporal  region,  and  the  bone  formed  from  this  center  subsequently  unites 
with  the  petrous  part  and  becomes  the  temporal  squama.  Another  center  ap- 
pears in  the  membrane  to  the  outer  side  of  the  periotic  capsule  and  produces  a 
ring  of  bone  around  the  external  auditory  meatus,  which  fuses  with  the  petrous 


Parietal 


Occipital 

fontanelle 


Occipital  ~ 


Mastoid   - 
fontanelle 


Occipital 

Petrous 

Occipital 

Tympanic 

Styloid  process 

Stylohyoid  lig. . 

Hyoid  (greater  horn)  . 


Cricoid 


Mandible 

Meckel's  cartilage 
Hyoid  (lesser horn) 

Thyreoid 


FIG.  177. — Diagram  of  skull  of  new-born  child.     Combined  from  McMurrich  and  Kollmann. 
White  areas  represent  bones  of  intramembranous  origin;  dotted  areas  represent  bones  (not  derived 
from    branchial  arches)  of  intracartilaginous  origin;    black  areas   represent  derivatives  of 
branchial  arches. 


part  and  forms  the  tympanic  part  of  the  adult  bone.  It  gives  attachment  at  its 
inner  border  to  the  tympanic  membrane.  While  the  union  of  the  different 
parts  begins  during  foetal  life,  it  is  usually  completed  after  birth. 

The  sphenoid  bone  is  also  composed  of  parts  which  have  different 
origins.  The  body,  small  wings  and  large  wings  are  of  intracartilaginous 
origin,  the  pterygoid  process  of  intramembranous  origin.  About  the  eighth 
week  of  development  a  center  of  ossification  appears  in  the  mesenchyme  in  the 
lateral  wall  of  the  posterior  part  of  the  nasal  cavity  and  gives  rise  to  the  medial 
pterygoid  lamina.  On  the  tip  of  the  latter  a  small  piece  of  cartilage  appears  in 


198  TEXT-BOOK  OF  EMBRYOLOGY. 

which  ossification  later  takes  place  to  form  the  pterygoid  hamulus  (p.  195). 
The  lateral  pterygoid  lamina  is  also  of  intramembranous  origin  and  fuses  with 
the  medial  lamina,  the  two  laminae  forming  the  pterygoid  process  which  subse- 
quently unites  with  the  body  of  the  sphenoid.  (See  Fig.  176.) 

In  the  ethmoidal  region,  only  the  vomer  is  of  intramembranous  origin.  An 
ossification  center  appears  in  the  embryonic  connective  tissue  on  each  side  of 
the  perpendicular  plate  (lamina  perpendicularis)  and  these  two  centers  produce 
two  thin  plates  of  bone  which  unite  at  their  lower  borders  and  invest  the  lower 
part  of  the  perpendicular  plate.  The  portion  of  the  latter  thus  invested 
undergoes  resorption. 

The  frontal  and  parietal  bones  are  purely  of  intramembranous  origin.  About 
the  eighth  week  two  centers  of  ossification,  one  on  each  side,  appear  for  the 
frontal.  The  bones  produced  by  these  centers  unite  in  the  medial  line  to  form 
the  single  adult  bone.  In  the  event  of  an  incomplete  union  an  open  suture 
remains — the  metopic  suture.  A  single  center  of  ossification  appears  for  each 
parietal  bone  at  about  the  same  time  as  those  for  the  frontal.  The  union  of 
the  bones  which  form  the  roof  and  the  greater  part  of  the  sides  of  the  skull  does 
not  occur  till  after  birth.  The  spaces  between  them  constitute  the  sutures  and 
fontanelles  so  obvious  in  new-born  children  (Fig.  177). 

A  single  center  of  ossification  appears  in  the  embryonic  connective  tissue 
for  each  zygomatic,  lachrymal  and  nasal  bone,  all  of  which  are  of  intramem- 
branous origin. 

BONES  DERIVED  FROM  THE  BRANCHIAL  ARCHES. 

The  first  branchial  arch  becomes  divided  into  two  portions.  One  of  these, 
the  maxillary  process,  is  destined  to  give  rise  to  the  upper  jaw  and  much  of  the 
upper  lip  and  face  region.  The  other,  the  mandibular  process,  is  destined  to 
give  rise  to  the  lower  jaw,  the  lower  lip  and  chin  region,  and  two  of  the  auditory 
ossicles.  The  angle  between  the  two  processes  corresponds  to  the  angle  of  the 
mouth,  and  the  cavity  enclosed  by  the  processes  is  the  forerunner  of  the  mouth 
and  nasal  cavities.  (See  Fig.  134,  also  p.  151.)  So  far  as  the  skeletal  elements 
are  concerned,  cartilage  develops  only  in  the  mandibular  process  where  it 
forms  a  slender  bar  or  rod  known  as  Meeker s  cartilage.  Only  a  small  part  of 
this  becomes  ossified,  the  greater  portion  of  the  mandible  being  of  intramem- 
branous origin.  No  cartilage  develops  in  the  maxillary  process.  This 
probably  indicates  a  condensation  of  development  in  man  and  the  higher 
animals,  for  among  the  lower  animals  cartilage  precedes  the  bone.  In  man  the 
maxilla  and  palate  bone  also  are  of  intramembranous  origin. 

The  palate  bone  develops  from  a  single  center  of  ossification  which  appears 
at  the  side  of  the  nasal  cavity  in  embryos  of  about  18  mm.  This  center 


THE   CONNECTIVE   TISSUES   AND   THE   SKELETAL  SYSTEM. 


199 


represents  the  perpendicular  part,  the  horizontal  part  appearing  in  embryos  of 
about  24  mm.  as  an  outgrowth  from  the  perpendicular  and  not  as  a  separate 
center  of  ossification.  The  orbital  and  sphenoidal  processes  also  represent  out- 
growths from  the  primary  center  and  appear  much  later. 

Opinions  regarding  the  development  of  the  maxilla  are  at  variance.  One 
view  is  that  it  arises  from  five  centers  of  ossification.  One  of  these  centers  gives 
rise  to  that  part  of  the  alveolar  border  which  bears  the  molar  and  premolar 
teeth;  a  second  center  forms  the  nasal  process  and  that  part  of  the  alveolar  bor- 
der which  bears  the  canine  tooth;  a  third  produces  the  part  which  bears  the 
incisor  teeth;  and  the  two  remaining  centers  give  rise  to  the  rest  of  the  bone. 
All  these  parts  effect  a  firm  union  at  an  early  stage,  with  the  exception  of  the 
part  bearing  the  incisor  teeth  which  remains  more  or  less  distinct  as  the  incisive 
bone  (premaxilla,  intermaxilla) .  Another  view  arising  from  recent  work  on 


Incisive  bone  Upper  lip 

(intermaxillary) 


Primitive  choanae 


Lip  groove 


Cut  surface          Palatine  processes 

FIG.  178. — Head  of  human  embryo  of  7  weeks.     His. 
Ventral  aspect  of  upper  jaw  region.     Lower  jaw  and  tongue  have  been  removed. 


human  embryos  is  that  there  are  primarily  only  two  ossification  centers;  one  of 
these  gives  rise  to  the  incisive  bone,  the  other  to  the  rest  of  the  maxilla  (Mall). 
These  centers  appear  at  the  end  of  the  sixth  week  (embryos  of  18  mm.). 

A  very  important  feature  in  the  development  of  the  maxilla  is  its  agency  in 
separating  the  nasal  cavity  from  the  mouth  cavity.  The  palatine  process  of  the 
bone  grows  medially  and  meets  and  fuses  with  its  fellow  of  the  opposite  side  in 
the  medial  line,  the  two  processes  together  thus  constituting  about  the  an- 
terior three-fourths  of  the  bony  part  of  the  hard  palate.  It  should  be  observed, 
however,  that  the  palatine  processes  do  not  meet  at  their  anterior  borders,  for 
the  incisive  bone  is  insinuated  between  them  (see  Figs.  178,  179). 


200 


TEXT-BOOK  OF  EMBRYOLOGY. 


The  incisive  bone  is  probably  not  derived  from  the  maxillary  process  of  the  first  visceral 
arch,  but  from  the  fronto-nasal  process.  The  question  thus  arises  as  to  whether  it  is  derived 
from  both  the  middle  and  lateral  nasal  processes  or  only  from  the  middle.  According  to 
Kolliker's  view,  the  lateral  nasal  process  takes  no  part  in  the  formation  of  the  incisive  bone. 
It  is  derived  from  the  middle  process,  hence  genetically  it  is  a  single  bone  on  each  side. 
According  to  Albrecht's  view  the  incisive  bone  is  genetically  composed  of  two  parts,  one 
derived  from  the  lateral,  the  other  from  the  middle  nasal  process.  While  the  matter  is  not 
one  of  great  importance  merely  from  the  standpoint  of  development,  it  has  an  important 
bearing  on  the  question  of  certain  congenital  malformations,  e.g.,  hare  lip,  and  will  be 
discussed  further  under  that  head  (p.  216). 

In  the  mandibular  process  of  the  first  visceral  arch,  the  mandible  develops  as 
a  bone  which  is  partly  of  intramembranous  and  partly  of  intracartilaginous 
origin.  In  the  first  place  a  rod  of  cartilage,  known  as  Meckel's  cartilage, 
forms  the  core  of  the  mandibular  process  and  extends  from  the  distal  end  of  the 
process  to  the  temporal  region  of  the  skull,  where  it  passes  between  the  tympanic 


Medial  line 
Canine  alveolus 


Molar  alveolus 


Palate  bone 
(horizontal  part) 


FIG.  179. — Ventral  aspect  of  hard  palate  of  human  embryo  of  80  mm.     Kollmann's  Atlas. 


bone  and  the  periotic  capsule  and  ends  in  the  tympanic  cavity  of  the  ear  (Fig. 
174).  During  the  sixth  week  of  fcetal  life,  intramembranous  bone  begins  to 
develop  in  the  mandibular  process.  In  the  region  of  the  body  of  the  mandible 
the  bone  encloses  the  cartilage,  but  in  the  region  of  the  ramus  and  coronoid 
process  the  cartilage  lies  to  the  inner  side  of  the  bone.  Development  is  further 
complicated  by  the  appearance  of  cartilage  in  the  region  of  the  middle  incisor 
teeth  and  on  the  coronoid  and  condyloid  processes.  These  pieces  of  cartilage 
form  independently  of  Meckel's  cartilage  and  subsequently  are  replaced  by  the 
bone  which  constitutes  the  corresponding  parts  of  the  mandible.  The  part  of 
Meckel's  cartilage  enclosed  in  the  bone  disappears;  the  part  to  the  inner  side  of 
the  ramus  is  transformed  into  the  sphenomandibular  ligament.  (See  Fig.  180.) 
In  each  half  of  the  second  branchial  arch  a  rod  of  cartilage  develops,  which 
extends  from  the  ventro-medial  line  to  the  region  of  the  periotic  capsule.  The 


THE   CONNECTIVE   TISSUES   AND   THE   SKELETAL  SYSTEM.  201 

proximal  end  of  this  rod  is  then  replaced  by  bone  which  fuses  with  the  temporal 
bone  and  forms  the  styloid  process.  The  distal  (ventral)  end  is  replaced  by 
bone  which  forms  the  lesser  horn  of  the  hyoid  bone.  Between  the  styloid  proc- 
ess and  the  lesser  horn,  the  cartilage  is  transformed  into  the  stylohyoid  liga- 
ment (see  Figs.  177  and  180). 

In  each  half  of  the  third  branchial  arch  a  piece  of  cartilage  develops  and 
subsequently  is  replaced  by  bone  to  form  the  greater  horn  of  the  hyoid  bone. 
The  two  horns  become  connected  at  their  ventral  ends  by  the  body  of  the  hyoid 
bone  which  is  also  a  derivative  of  the  third  arch.  Later  the  lesser  horn  fuses 
with  the  greater  horn  to  bring  about  the  adult  condition  (Fig.  180). 

In  the  ventral  parts  of  the  fourth  and  fifth  arches  pieces  of  cartilage  develop 

Incus       Malleus 


Mandible 

Tympanic  ring 

Stylohyoid  lig. 
Cricoid  cartilage 

Thyreoid  cartilage      |  Meckel's  cartilage 

Hyoid  cartilage  (greater  horn) 

FIG.  180. — Lateral  dissection  of  head  of  human  foetus,  showing  derivatives  of  branchial 
arches  in  natural  position.     Kollmann's  Atlas. 

and  form  the  skeletal  elements  of  the  larynx.  A  more  detailed  account  of  these 
will  be  found  under  the  head  of  the  larynx  (p.  363). 

The  auditory  ossicles  are  also  derived  largely  from  the  branchial  arches,  the 
incus  and  malleus  being  derived  from  the  proximal  end  of  Meckel's  cartilage  (first 
arch) ,  the  stapes  having  a  double  origin  from  the  second  arch  and  the  embryonic 
connective  tissue  surrounding  the  periotic  capsule.  But  since  they  form  inte- 
gral parts  of  the  organ  of  hearing,  a  discussion  of  their  formation  is  best  in- 
cluded in  the  development  of  the  ear  (p.  599). 

The  accompanying  table  indicates  the  types  of  development  in  the  different 
bones  of  the  head  skeleton. 


202 


TEXT-BOOK  OF  EMBRYOLOGY. 


Bones 

Of  Intracartilaginous 
Origin 

Of  Intramembranous 
Origin 

Derived  from  Visceral 
Arches 

Occipitale. 

Pars  basilaris. 
Pars  lateralis. 
Squama  occipitalis  below 
sup.  nuchal  line. 

Squama  occipitalis  above 
sup.  nuchal  line. 

Temporale. 

Pars  mastoidea. 
Pars    petrosa,   with   proc- 
essus  styloideus. 

Pars  tympanica. 
Squama  temporalis. 

Processus  styloideus  (second 
arch). 

Sphenoidale. 

Corpus. 
Ala  parva. 
Ala  magna. 
Hamulus  pterygoideus. 

Processus  pterygoideus,  ex- 
cept hamulus    pterygoi- 
deus. 

Ethmoidale. 

Crista  galli. 
Lamina  cribrosa. 
Lamina  perpendicularis. 
Labyrinthus  ethmoidalis. 

Vomer. 

Vomer. 

Parietale. 

Parietale. 

Frontale. 

Frontale. 

Lacrimale. 

Lacrimale. 

Nasale. 

Nasale. 

Zygoma. 

Zygoma. 

Maxilla. 

Maxilla,  with  incisivum. 

Maxilla,exceptincisivum(  ?) 
(first  arch). 

Palatinum. 

Palatinum. 

Palatinum. 

Mandibula. 

Processus    condyloideus, 
tip  of. 
Processus  coronoideus, 
tip  of. 
Corpus,  distal  end  of. 

Processus  condyloideus,  ex- 
cept tip. 
Processus  coronoideus,  ex- 
cept tip. 
Corpus,  except  distal  end. 
Ramus 

Mandibula  (first  arch). 

Hyoideum. 

Hyoideum 

Cornu  majus  (third  arch). 
Cornu  minus  (second  arch). 
Corpus  (third  arch). 

Ossicula 
auditus. 

Incus. 
Malleus. 
Stapes,  except  basis  (?). 

Basis  stapedis. 

Incus  (first  arch). 
Malleus   (first  arch). 
Stapes,     except     basis     (?) 
(second  arch). 

The  Appendicular  Skeleton. 

The  growth  of  the  limb  buds  and  their  differentiation  into  arm,  forearm 
and  hand,  thigh,  leg  and  foot,  along  with  the  rotation  which  they  undergo  during 
development,  have  been  discussed  in  the  chapter  on  the  external  form  of  the 
body  (p.  153).  The  metameric  origin  of  the  muscles  of  the  extremities  is 


THE   CONNECTIVE  TISSUES   AND   THE   SKELETAL  SYSTEM. 


203 


discussed  in  the  chapter  on  the  muscular  system  (Chap.  XI).  It  has  been 
seen  that  the  greater  part  of  the  axial  skeleton  is  derived  from  the  sclerotomes, 
is  preformed  in  cartilage,  and  maintains  its  segmental  character  throughout  life. 
It  has  also  been  seen  that  the  head  skeleton  is  in  part  preformed  in  cartilage,  is  in 
part  of  intramembranous  origin,  and  shows  but  a  trace  of  segmental  character, 
and  that  only  in  the  occipital  region  at  a  very  early  stage.  The  appendicular 
skeleton  is  derived  wholly  from  the  embryonic  connective  tissue  which  forms  the 
cores  of  the  developing  extremities,  and  shows  no  trace  of  a  segmental  character. 
Here  also,  as  in  the  axial  skeleton,  three  stages  may  be  recognized — a  blastemal, 
a  cartilaginous  (Fig.  181),  and  a  final  osseous. 

Acromion        Coracoid  process 


Scapula 


Humerus 


Radius 

Metacarpal  I 

Large  multangular 
(trapezium) 

Navicular  (scaphoid) 
Lunate  (semilunar) 

Small  multangular 
(trapezoid) 

Metacarpal  IV 
Capitate  (os  magnum) 
Triquetral  (cuneiform) 
Hamatate  (unciform) 


Ulna 


FIG.  181. — Cartilages  of  left  upper  extremity  of  a  human  embryo  of  17  mm.     Hagen. 

In  the  region  of  the  shoulder  girdle  a  plate  of  cartilage  appears  in  the  em- 
bryonic connective  tissue  which  lies  among  the  developing  muscles  dorso-lateral 
to  the  thorax.  This  plate  of  cartilage  is  the  forerunner  of  the  scapula,  and  in 
general  resembles  it  in  shape.  During  the  eighth  week  of  foetal  life  a  single 
center  of  ossification  appears  and  gives  rise  to  the  body  and  spine  of  the  scapula. 
After  birth  certain  accessory  centers  appear  and  produce  the  coracoid  process,  the 
supraglenoidal  tuberosity,  the  acromion  process,  and  the  inferior  angle  and  verte- 
bral margin  (Fig.  182).  Later  the  supraglenoidal  fuses  with  the  coracoid  and 
forms  part  of  the  wall  of  the  glenoid  cavity.  About  the  seventeenth  year  the 
single  center  formed  by  the  union  of  these  two  fuses  with  the  rest  of  the  scapula. 


204  TEXT-BOOK  OF  EMBRYOLOGY. 

At  the  age  of  twenty  to  twenty-five  years  all  the  other  accessory  centers  unite 
with  the  rest  of  the  scapula  to  form  the  adult  bone. 

There  are  two  views  concerning  the  development  of  the,  clavicle:  one  that  it 
is  of  intracartilaginous  origin,  the  other  that  it  is  of  intramembranous  origin. 
Ossification  begins  during  the  sixth  week,  possibly  from  two  centers.  It  is  true 
that  the  cartilage  that  appears  around  the  centers  is  of  a  looser  character  than 
the  ordinary  embryonic  cartilage,  but  whether  the  centers  appear  in  cartilage 
seems  not  to  have  been  determined.  At  the  age  of  fifteen  to  twenty  years  a 
sort  of  secondary  center  appears  at  the  sternal  end  of  clavicle  and  fuses  with 
the  body  about  the  twenty-fifth  year. 

The  humerus,  radius  and  ulna  are  preformed  in  cartilage  (Fig.  181)  and 
develop  as  typical  long  bones.  Ossification  begins  in  each  during  the  seventh 


Coracoid 
process  ~ 


Glenoidal 
fossa 


Bone 


Cartilage 


FlG.  182. — Scapula  of  new-born  child,  showing  primary  center  of  ossification,  and  cartilage 
(lighter  shading)  in  which  secondary  centers  appear.     Bonnet. 

week  at  a  single  center  and  proceeds  in  both  directions  to  form  the  shaft. 
During  the  first  four  years  after  birth  epiphyseal  centers  appear  for  the  head, 
greater  and  smaller  tubercles,  trochlea  and  epicondyles.  All  these  secondary 
centers  unite  with  the  shaft  of  the  humerus  when  the  growth  of  the  individual 
ceases.  In  the  case  of  the  radius  and  ulna  a  secondary  center  appears  at  each 
end  of  each  bone  to  form  the  epiphysis;  and  in  the  ulna  another  secondary 
center  appears  to  form  the  olecranon.  (For  the  growth  of  bones,  see  page  180). 
The  carpal  bones  are  all  preformed  in  cartilage  (Fig.  181)  but  their  develop- 
ment is  somewhat  complicated  owing  to  the  fact  that  pieces  of  cartilage  appear 
which  subsequently  may  disappear,  or  ossify  and  become  incorporated  in  other 
bones.  Primarily  seven  distinct  pieces  of  cartilage  develop  and  become  ar- 
ranged transversely  in  two  rows;  these  represent  seven  of  the  carpal  bones. 
The  proximal  row  consists  of  three  large  pieces  which  are  the  forerunners  of  the 
namcular  (radial,  scaphoid),  lunate  (intermediate,  semilunar)  and  triquetral 


THE   CONNECTIVE   TISSUES   AND   THE   SKELETAL  SYSTEM. 


205 


(ulnar,  pyramidal,  cuneiform).  The  distal  row  is  composed  of  four  elements 
which  are  the  forerunners  of  the  large  multangular  (trapezium),  small  multangu- 
lar (trapezoid) ,  capitate  (os  magnum) ,  and  hamatate  or  hooked  (unciform) .  In 
addition  to  the  cartilages  mentioned,  several  others  also  appear  in  an  inconstant 
way  in  different  individuals.  Two  of  these  are  important.  One  appears  on 
the  ulnar  side  of  the  proximal  row  and  is  the  forerunner  of  the  pisiform;  the 
other  is  situated  between  the  two  rows  and  may  either  disappear  entirely  or  fuse 
with  the  navicular.  Ossification  does  not  begin  in  the  carpal  cartilages  until 
after  birth;  it  begins  in  the  hamatate  and  capitate  during  the  third  year,  in  the 


Large 

multangular 

Capitate 

Navicular 

Radius 


Phalanges 

Metacarpals 

Hamatate 
Triquetral 
Lunate 
Ulna 


FIG.  183. — Skiagram  of  right  hand  of  5  year  old  girl.     (Courtesy  of  Dr.  Edward  Learning). 
The  ossification  centers  are  indicated  by  the  darker  areas. 

others  at  later  periods,  and  is  completed  only  when  the  growth  of  the  individ- 
ual ceases.  The  fact  that  the  hamatate  ossifies  from  two  centers  indicates 
that  it  is  probably  derived  phylogenetically  from  two  bones.  Comparative 
anatomy  teaches  that  the  accessory  cartilages  in  the  human  wrist  are  repre- 
sentatives of  structures  which  are  normally  present  in  the  lower  forms. 

The  metacarpals  and  phalanges  are  preformed  in  cartilages  which  correspond 
in  shape  to  the  adult  bones.  A  center  of  ossification  appears  in  each  cartilage 
and  produces  the  shaft  of  the  bone.  Only  one  epiphysis  develops  on  each 
metacarpal  and  phalanx.  In  each  metacarpal  it  develops  at  the  distal  end, 


206 


TEXT-BOOK  OF  EMBRYOLOGY. 


,  Crural  nerve 


Ilium    I 


Pubic  bone  (cartilage) 


ra5™"* —   Obturator  ne 


Ischium 


Ischiadic  nerve 


FIG.  184. — Cartilage  of  right  side  of  pelvic  girdle  of  a  human  embryo  of  13.6  mm. 

(5  weeks).     Petersen. 
The  numerals  indicate  the  vertebras;  the  first  sacral  being  opposite  the  ilium. 


Iliu: 


\ 


Crural  nerve 

—  Pubic  bone  (cartilage) 

Obturator  nerve 
Ischium 

Ischiadic  nerve 


FIG.  185. — Cartilage  of  right  side  of  pelvic  girdle  of  a  human  embryo  of  18.5  mm. 

(8  weeks).     Petersen. 

The  numerals  indicate  the  vertebrae;  the  first  and  second  sacral  being  opposite  the  ilium. 

Compare  with  Fig.  184. 


THE   CONNECTIVE   TISSUES   AND   THE   SKELETAL  SYSTEM.  207 

except  in  the  thumb  where  it  appears  at  the  proximal  end.     In  each  phalanx  it 
develops  at  the  proximal  end  (Fig.  183). 

The  skeletal  elements  of  the  lower  extremities,  including  the  pelvic  girdle,  are 
of  intracartilaginous  origin.  Each  hip  bone  (os  coxas,  innominate  bone)  is  pre- 
formed in  cartilage  which,  in  a  general  way,  resembles  in  shape  the  adult  bone. 
The  ventral  part  of  the  pubic  cartilage  does  not  at  first  join  the  ischial;  but  by  the 
eighth  week  the  junction  is  complete,  leaving  dorsal  to  it  the  obturator  foramen. 
In  the  earliest  stages  the  long  axis  of  the  cartilage  is  nearly  at  right  angles  to  the 
vertebral  column,  and  the  ilium  lies  close  to  the  fifth  lumbar  and  first  sacral 
vertebras;  later  (eighth  week)  the  long  axis  lies  nearly  parallel  with  the  vertebral 
column  and  the  whole  cartilage  has  shifted  so  that  the  ilium  is  associated  with 
the  first  three  sacral  vertebrae  (Figs.  184  and  185). 


Pubic  bone 


Ilium 


Cartilage 


FIG.  186  — Right  os  coxae  (innominate  bone)  of  new-born  child.     Bonnet. 
Bone  is  indicated  by  darker  areas,  cartilage  by  lighter  areas. 


Ossification  begins  at  three  centers  which  correspond  to  the  ilium,  ischium 
and  pubis;  the  center  for  the  ilium  appears  during  the  eighth  week,  the  centers 
for  the  ischium  and  pubis  several  weeks  later  (Fig.  186).  The  process  of  ossifi- 
cation is  slow,  and  is  far  from  complete  at  the  time  of  birth,  for  at  that  time  the 
entire  crest  of  the  ilium,  the  bottom  of  the  acetabulum  and  all  the  region  ventral 
to  the  obturator  foramen  are  cartilaginous.  During  the  eighth  or  ninth  year 
the  ventral  parts  of  the  pubis  and  ischium  become  partly  ossified,  but  up  to  the 
time  of  puberty  the  pubis,  ischium  and  ilium  remain  separated  by  plates  of  car- 
tilage which  radiate  from  a  common  center  at  the  bottom  of  the  acetabulum. 
Soon  after  this,  the  three  bones  unite  to  form  the  single  os  coxae,  leaving  only  the 
crest  of  the  ilium,  the  pubic  tubercle  and  the  sciatic  tuber  (tuberosity  of  the 
ischium)  cartilaginous.  In  each  of  these  regions  an  accessory  ossification  cen- 
14 


208 


TEXT-BOOK  OF  EMBRYOLOGY. 


ter  appears  and  finally  fuses  with  the  corresponding  bone  about  the  twenty- 
fourth  year. 

The  femur,  tibia  and  fibula  are  preformed  in  cartilage.  In  the  femur  a  center 
of  ossification  appears  about  the  end  of  the  sixth  week  and  gives  rise  to  the 
shaft;  similar  centers  appear  in  the  tibia  and  fibula  during  the  seventh  and 
eighth  week,  respectively.  In  the  femur  a  distal  epiphyseal  center  appears 
shortly  before  birth,  and  during  the  first  year  after  birth  a  proximal  center 
appears  for  the  head.  These  centers  do  not  unite  with  the  shaft  until  the  individ- 
ual ceases  to  grow.  The  great  and  lesser  trochanters  also  have  accessory  ossifica- 
tion centers.  In  the  tibia  the  center  of  ossification  for  the  proximal  epiphysis 
appears  about  the  time  of  birth,  the  one  for  the  distal  during  the  second  year.  In 


Fibul 


Calcaneus 


Cuboid 
Cuneiform  III 


Tibia 


Talus 

Navicular 

Cuneiform  I 
------ -Cuneiform  II 


Metatarsals 
FIG.  187. — Diagram  of  cartilages  of  left  leg  and  foot  of  human  embryo  of  17  mm.     Hagen. 


the  fibula  the  epiphyseal  centers  appear  during  the  second  and  sixth  years  after 
birth.  The  cartilage  of  the  patella  appears  during  the  third  or  fourth  month 
of  foetal  life,  and  ossification  begins  two  or  three  years  after  birth. 

The  bones  of  the  tarsus,  like  those  of  the  carpus,  are  preformed  in  pieces  of 
cartilage  which  are  arranged  in  two  transverse  rows.  The  proximal  row  con- 
sists of  three  pieces,  one  at  the  end  of  the  tibia  (tibial),  one  at  the  end  of  the 
fibula  (fibular),  and  the  third  between  the  two  (intermedial) .  At  an  early  stage 
the  tibial  and  intermedial  fuse  to  form  a  single  piece  of  cartilage  which  corre- 
sponds to  the  talus  (astragalus)  bone.  The  fibular  cartilage  corresponds  to  the 
calcaneus  (os  calcis).  The  distal  row  is  composed  of  four  pieces  of  cartilage 
which  correspond  to  the  first  cuneiform  (internal),  second  cuneiform  (middle), 
third  cuneiform  (external),  and  cuboid  (Fig.  187).  Between  the  two  rows  is  a 


THE   CONNECTIVE   TISSUES   AND   THE   SKELETAL  SYSTEM. 


209 


piece  of  cartilage  which  corresponds  to  the  navicular  (scaphoid).  Ossification 
begins  relatively  late  in  the  metatarsals.  A  center  for  the  calcaneus  appears 
during  the  sixth  month  of  fcetal  life,  and  one  for  the  talus  shortly  before  birth. 
Centers  appear  in  the  cuboid  and  third  cuneiform  during  the  first  year  after 
birth,  and  in  the  first  cuneiform,  navicular  and  second  cuneiform  in  order  during 
the  third  and  fourth  years  (Figs.  188  and  189).  At  the  age  of  puberty  ossifica- 
tion is  nearly  complete  in  all  the  metatarsals.  In  the  talus  two  centers,  cor- 
responding to  the  tibial  and  intermedial,  appear,  but  soon  fuse  into  a  single 
center.  Occasionally  the  intermedial  remains  separate  and  forms  the  trigonum. 


Phalang 


FIG.  188. — Ossification  centers  in  foot  of  a  child  9  months  old.     Hassel-wander. 

An  accessory  center  appears  in  the  calcaneus  at  the  insertion  of  the  tendon  of 
Achilles. 

The  metatarsals  and  phalanges  develop  in  a  manner  corresponding  to  the 
metacarpals  and  phalanges  (of  fingers).  Ossification  begins  in  the  metatarsals 
about  the  ninth  week,  in  the  first  row  of  (proximal)  phalanges  about  the 
thirteenth  week,  in  the  second  row  about  the  sixteenth  week  and  in  the  third 
row  (distal)  about  the  beginning  of  the  ninth  week.  Epiphyseal  centers  ap- 
pear from  the  second  to  the  eighth  year  after  birth. 

Development  of  Joints. 

The  embryonic  connective  tissue  from  which  the  connective  tissues,  includ- 
ing cartilage  and  bone,  are  developed,  at  first  forms  a  continuous  mass.  When 
cartilage  appears  it  may  form  a  continuous  mass,  as  in  the  chondrocranium,  or 


210 


TEXT-BOOK  OF  EMBRYOLOGY. 


it  may  form  a  number  of  distinct  and  separate  pieces,  as  in  the  vertebral  column, 
the  pieces  being  united  by  a  certain  amount  of  the  undifferentiated  embryonic 
connective  tissue. 

SYNARTHROSIS.  Syndesmosis. — When  ossification  begins  at  one  or  more 
centers,  either  in  cartilage  or  in  embryonic  connective  tissue,  the  centers  grad- 
ually enlarge  and  approach  each  other,  and  the  bone  so  formed  comes  in  contact 
with  the  bone  formed  in  neighboring  centers,  (a)  In  a  case  where  more  than  one 
center  appears  for  any  single  adult  bone,  they  may  come  in  contact  and  fuse  so 
completely  that  the  line  of  fusion  becomes  indistinguishable,  (b)  In  the  case  of 


Calcaneus  -    !    TO! 
(os  calcis)        \fi 


Cuboid      ~ 


Metatarsal  V 


Epiphysis  of  — »-.  i    i 
metatarsal  V 


Talus  (astragalus) 


Cuneiform  II 


Cuneiform  I 

Epiphysis  of 
metatarsal  I 


Metatarsal  I 


Epiphyses  of 
phalanges 


FIG.  189. — Skeleton  of  right  foot  of  a  boy  3  years  old,  showing  ossification  centers.     Toldt. 

adjacent  bones  the  fusion  may  not  be.  so  complete ;  that  is,  the  two  bones  may 
simply  articulate,  leaving  a  visible  line  of  junction  or  suture.  Such  joints  are 
immovable  and  are  represented  in  the  sutures  of  the  skull. 

Synchondrosis. — In  some  cases  a  small  amount  of  embryonic  connective 
tissue  remains  between  adjacent  bones,  (a)  In  time,  this  embryonic  connective 
tissue  gives  rise  to  cartilage  which  unites  the  bones  quite  firmly,  thus  producing 
a  practically  immovable  joint,  as  in  the  case  of  the  sacro-iliac  joint,  (b)  Or  the 
cells  in  the  center  of  the  cartilage  disintegrate  or  become  liquefied  so  that  a  small 
cavity  is  produced  (articular  cavity).  This  type  of  joint  makes  possible  a  slight 
degree  of  mobility  and  is  exemplified  by  the  symphysis  of  the  pubic  bones.  Such 
a  type  is  also  represented  by  the  joints  of  the  vertebral  column.  In  place  of 
cavities,  however,  are  the  pulpy  nuclei  which  are  remnants  of  the  notochord. 


THE   CONNECTIVE   TISSUES  AND   THE   SKELETAL  SYSTEM. 


211 


DIARTHROSIS. — Where  a  great  degree  of  mobility  is  necessary,  the  arrange- 
ment of  the  joint  is  different.  The  cells  in  the  central  part  of  the  embryonic 
connective  tissue  between  the  ends  of  adjacent  bones  (or  cartilages)  (Fig.  190) 
liquefy  so  that  a  relatively  large  cavity,  the  joint  cavity,  is  formed  (Fig.  191). 
The  liquefaction  of  the  connective  tissue  cells  may  also  extend  for  a  short  dis- 
tance along  the  sides  of  the  bones  so  that  the  joint  cavity  surrounds  the  ends 
of  the  bones  (Figs.  192  and  193).  The  origin  of  the  synovial fluid  is  not  known 


Humerus 


.'"    ' 


fe   •;. 

/'          ^-.••••r'.'P* '  '.'••':'&;.'. 


Radius 

FIG.  190. — Section  through  axilla  and  arm  of  a  human  embryo  of  26  mm.  (2  months).     Photograph. 
Note  the  mesenchymal  tissue  between  the  humerus  and  the  radius — the  site  of  the  elbow  joint. 

with  certainty,  but  it  is  probably  in  part  the  product  of  liquefaction  of  the  con- 
nective tissue  cells.  The  more  peripheral  part  of  the  connective  tissue  which 
encloses  the  joint  cavity  is  transformed  into  a  dense  fibrous  tissue,  the  joint 
capsule.  The  cells  lining  the  cavity  become  differentiated  into  oval  or  irregular 
cells,  among  which  is  a  considerable  amount  of  intercellular  substance.  By. 
some  it  is  held  that  these  cells  form  a  continuous  single  layer  like  endothelium, 
but  the  most  recent  researches  tend  to  disprove  this.  The  cells  lining  the 


212 


TEXT-BOOK  OF  EMBRYOLOGY. 


Joint  cavity 


FIG.  191. — Longitudinal  section  of  finger  of  human  embryo  of  26  mm.  (2  months),  showing  beginning 
of  joint  cavity  between  adjacent  ends  of  phalanges.  (Photograph  from  preparation  by 
Dr.  W.  C.  Clarke.) 


FIG.  192. — From  longitudinal  section  of  finger  of  child  at  birth,  showing  developing  joint  cavity 
between  adjacent  ends  of  phalanges.  The  darker  portion  at  each  end  of  the  figure  indicates 
the  ossification  center  in  the  phalanx,  the  end  of  the  latter  (lighter  area)  being  yet  cartilagi- 
nous. The  dark  bands  at  each  side  of  the  joint  indicate  developing  ligaments.  Photograph. 


THE   CONNECTIVE   TISSUES   AND   THE   SKELETAL  SYSTEM. 


213 


cavity  are  the  most  highly  differentiated,  the  cell  bodies  being  large  and  ap- 
parently swollen,  and  there  is  gradually  less  differentiation  as  the  distance  from 
the  surface  increases,  until  finally  they  merge  with  the  ordinary  type  of  con- 
nective tissue  cells  of  the  joint  capsule  (Clarke).  The  more  mobile  joints  of 
the  body  are  all  representatives  of  this  type. 

Joint  cavity 


Synovial  membrane 

FiG.  193. — From  longitudinal  section  of  finger  of  child  at  birth,  showing  joint  cavity  and  synovial 
membrane  between  adjacent  ends  of  the  first  metacarpal  and  proximal  phalanx.  Other 
description  same  as  in  Fig.  192.  Photograph. 

Anomalies. 
THE  AXIAL  SKELETON. 

THE  VERTEBRA. — The  number  of  cervical  vertebrae  in  man  is  remarkably 
constant.  Cases  where  the  number  is  but  six  are  extremely  rare.  The 
thoracic  vertebras  may  vary  in  number  in  different  individuals  from  eleven  to 
thirteen,  twelve  being  the  usual  number.  The  lumbar  vertebrae  may  vary 
from  four  to  six,  five  being  the  usual  number.  The  sacral  vertebrae,  fused  in  the 
adult  to  form  the  sacrum,  are  usually  five  in  number,  sometimes  four,  sometimes 


214  TEXT-BOOK  OF  EMBRYOLOGY. 

six.  Occasionally  a  vertebra  between  the  lumbar  region  and  sacral  region — 
lumbo-sacral  vertebra — possesses  both  lumbar  and  sacral  characters,  one 
side  being  fused  with  the  sacrum,  the  other  side  having  a  free  transverse  process. 
Variation  occurs  frequently  in  the  coccygeal  vertebrae;  four  and  five  are  present 
with  about  equal  frequency,  more  rarely  there  are  only  three. 

The  total  number  of  true  (presacral)  vertebrae  may  be  diminished  by  one  or 
increased  by  one.  In  the  former  case  the  first  sacral  is  the  twenty-fourth  ver- 
tebra, and,  if  the  number  of  ribs  remains  normal,  there  are  only  four  lumbar 
vertebras.  In  case  the  total  number  is  increased  by  one,  the  first  sacral  is  the 
twenty-sixth  vertebra,  and  there  are  twelve  thoracic  and  six  lumbar  or  thirteen 
thoracic  and  five  lumbar. 

From  these  facts  it  is  seen  that  variation  occurs  most  frequently  in  the  more 
caudal  portion  of  the  vertebral  column — in  the  lumbar,  sacral  and  coccygeal 
regions.  According  to  a  hypothesis  advanced  by  Rosenberg,  the  sacrum  in  the 
earlier  embryonic  stages  is  composed  of  a  more  caudal  set  of  vertebrae  than  those 
which  belong  to  it  in  the  adult,  and  during  development  lumbar  vertebrae  are 
converted  into  sacral  and  sacral  vertebrae  into  coccygeal.  In  other  words,  the 
hip  bone  moves  headward  during  development  and  finally  becomes  attached  to 
vertebras  which  are  situated  more  cranially  than  those  with  which  it  was  pri- 
marily associated.  This  change  in  the  position  of  the  pelvic  attachment,  and  the 
corresponding  reduction  in  the  total  number  of  vertebrae,  during  the  develop- 
ment of  the  individual  (i.e.,  during  ontogenetic  development)  is  believed  to 
correspond  to  a  similar  change  in  position  during  the  evolution  of  the  race  (i.e., 
during  phylogenetic  development). 

According  to  Rosenberg,  variation  in  the  adult  is  due  largely  to  a  failure 
during  ontogeny  to  carry  the  processes  of  reduction  in  the  number  of  vertebrae 
as  far  as  they  are  usually  carried  in  the  race,  or  to  their  being  carried  beyond  this 
point. 

The  coccygeal  vertebrae  apparently  represent  remnants  of  the  more  exten- 
sively developed  caudal  vertebrae  in  lower  forms.  In  human  embryos  of  8  to 
16  mm.,  when  the  caudal  appendage  is  at  the  height  of  its  development,  there 
are  usually  seven  anlagen  of  coccygeal  vertebrae.  During  later  development  this 
number  becomes  reduced  by  fusion  of  the  more  distally  situated  anlagen  to  the 
smaller  number  in  the  adult.  This  process  of  reduction  varies  in  different  in- 
dividuals, so  that  five  or  four,  rarely  three,  coccygeal  vertebrae  may  be  the  result. 
In  cases  where  children  are  born  with  distinct  caudal  appendages  there  is  no 
good  evidence  that  the  number  of  coccygeal  vertebrae  is  increased,  although  the 
coccyx  may  extend  into  the  appendage. 

THE  RIBS. — Occasionally  in  the  adult  a  rib  is  present  on  one  side  or  on 
each  side  in  connection  with  the  seventh  cervical  vertebra  (cervical  rib),  or  in 
connection  with  the  first  lumbar  vertebra  (lumbar  rib).  There  seems  to  be  no 


THE   CONNECTIVE   TISSUES   AND   THE   SKELETAL  SYSTEM.  215 

case  on  record  where  cervical  and  lumbar  ribs  are  present  in  the  same  individual. 
The  cervical  rib  may  vary  between  a  small  piece  of  bone  connected  with  the 
transverse  process  of  the  vertebra  and  a  well  developed  structure  long  enough  to 
reach  the  sternum.  There  are  also  great  variations  in  the  size  of  the  lumbar  rib. 
In  case  the  number  of  ribs  is  normal,  the  last  (twelfth)  may  be  rudimentary. 

The  eighth  costal  cartilage  not  infrequently  unites  with  the  sternum.  Oc- 
casionally the  seventh  costal  cartilage  fails  to  fuse  with  the  sternum,  owing  to 
the  shortening  of  the  latter,  but  meets  and  fuses  with  its  fellow  of  the  opposite 
side  in  the  midventral  line. 

The  above  mentioned  anomalies  can  be  referred  back  to  aberrant  develop- 
ment. Primarily  costal  processes  appear  in  connection  with  the  cervical,  lum- 
bar and  sacral  vertebras.  Normally  these  processes  fuse  with  and  finally  form 
parts  of  the  vertebrae  (p.  189).  In  some  cases,  however,  the  seventh  cervical  or 
the  first  lumbar  processes  develop  more  fully  and  form  more  or  less  distinct  ribs. 

As  an  explanation  of  these  variations  in  the  number  of  ribs,  it  has  been  sug- 
gested that  there  is  a  tendency  toward  reduction  in  the  total  number  of  ribs,  and 
that  supernumerary  ribs  represent  the  result  of  a  failure  to  carry  the  reduction  as 
far  as  the  normal  number.  In  case  the  twelfth  rib  is  rudimentary,  the  reduction 
has  been  carried  beyond  the  normal  limit.  This  hypothesis  is  a  corollary  to  the 
hypothesis  regarding  the  variations  in  the  number  of  vertebrae.  (See  under 
"The  Vertebras.") 

THE  STERNUM. — Certain  anomalous  conditions  of  the  sternum  can  also  be 
explained  by  reference  to  development.  The  condition  known  as  cleft  sternum, 
in  which  the  sternum  is  partially  or  wholly  divided  into  two  longitudinal  bars 
by  a  medial  fissure,  represents  the  result  of  a  failure  of  the  two  bars  to  unite  in 
the  midventral  line  (p.  189,  see  also  Fig.  168).  This  is  sometimes  associated 
with  ectopia  cordis  (p.  285).  The  xyphoid  process  may  also  be  bifurcated  or 
perforated,  according  to  the  degree  of  fusion  between  the  two  primary  bars 
(p.  190). 

Supr asternal  bones  may  be  present.  They  represent  the  ossified  episternal 
cartilages  which  have  failed  to  unite  with  the  manubrium  (p.  190).  Morpho- 
logically the  suprasternal  bones  possibly  represent  the  omosternum,  a  bone 
situated  cranially  to  the  manubrium  in  some  of  the  lower  Mammals. 

THE  HEAD  SKELETON. — The  skull  is  sometimes  decidedly  asymmetrical. 
Probably  no  skull  is  perfectly  symmetrical.  The  condition  which  most  fre- 
quently accompanies  the  irregular  forms  of  skulls  is  premature  synosteosis  or 
premature  closure  of  certain  sutures.  The  cranial  bones  increase  in  size  prin- 
cipally at  their  margins,  and  when  a  suture  is  prematurely  closed  the  growth  of 
the  skull  in  a  direction  at  right  angles  to  the  line  of  suture  is  interfered  with. 
Consequently  compensatory  growth  must  take  place  in  other  directions.  Thus 
if  the  sagittal  suture  is  prematurely  closed  and  transverse  growth  prevented, 


216  TEXT-BOOK  OF  EMBRYOLOGY. 

increase  occurs  in  the  vertical  and  longitudinal  directions.  This  results  in  the 
vault  of  the  skull  becoming  heightened  and  elongated,  like  an  inverted  skiff,  a 
condition  known  as  scaphocephaly.  After  premature  closure  of  the  coronal 
suture,  growth  takes  place  principally  upward  and  gives  rise  to  acrocephaly.  In 
case  only  one-half  the  coronal  or  lambdoidal  suture  is  closed,  the  growth  is 
oblique  and  results  in  plagiocephaly. 

A  suture — the  metopic  suture — sometimes  exists  in  the  medial  line  between 
the  two  halves  of  the  frontal  bone,  a  condition  known  as  metopism.  This  is  due 
to  an  imperfect  union  of  the  two  plates  of  bone  produced  by  the  two  centers  of 
ossification  in  the  frontal  region  (p.  198). 

Certain  malformations  in  the  face  region  and  in  the  roof  of  the  mouth  are 
brought  about  by  defective  fusion  or  complete  absence  of  fusion  between  certain 
structures  during  the  earlier  embryonic  stages.  The  maxillary  process  of  the 
first  branchial  arch  sometimes  fails  to  unite  with  the  middle  nasal  process 
(Kolliker's  view,  p.  200;  see  also  Fig.  136).  The  result  is  a  fissure  in  the 
upper  lip,  a  condition  known  as  hare  lip,  which  may  or  may  not  be  accompanied 
by  a  cleft  in  the  alveolar  process  of  the  maxilla,  extending  as  far  as  the  incisive 
(palatine)  foramen.  The  same  result  may  be  produced  by  a  defective  fusion 
between  the  middle  nasal  process  and  the  lateral  nasal  process  (Albrecht's  view, 
p.  200-;  see  also  Fig.  136).  Hare  lip  may  be  either  unilateral  (single)  or  bilateral 
(double),  accordingly  as  defective  fusion  occurs  on  one  or  both  sides,  but  never 
medial. 

Occasionally  the  palatine  process  of  the  maxillary  process  fails  to  meet  not 
only  its  fellow  of  the  opposite  side,  but  also  the  vomer  (see  Fig.  1 79) .  The  result 
is  a  cleft  in  the  hard  palate,  a  condition  known  as  cleft  palate.  This  malforma- 
tion may  be  unilateral  or  bilateral,  but  not  medial.  Sometimes  the  cleft  extends 
into  the  soft  palate  where  it  occupies,  however,  a  medial  position. 

Cleft  palate  may  accompany  hare  lip,  or  either  may  exist  without  the  other, 
depending  upon  the  degree  of  fusion  between  the  processes  mentioned  above. 
In  bilateral  hare  lip,  with  or  without  cleft  palate,  the  incisive  (intermaxillary) 
bone  is  sometimes  pushed  forward  by  the  vomer  and  projects  beyond  the  surface 
of  the  face,  a  condition  known  as  "wolf's  snout." 

The  causes  underlying  the  origin  of  hare  lip  and  cleft  palate  are  very  obscure. 

THE  APPENDICULAR  SKELETON. 

THE  HUMERUS. — On  the  medial  side  of  the  humerus,  just  proximal  to  the 
medial  condyle,  there  is  not  infrequently  a  small  hook-like  process  directed 
distally — the  supracondyloid  process.  This  process  represents  a  portion  of  bone 
which  in  some  of  the  lower  mammals  (cat,  for  example)  joins  the  internal 
condyle  and  completes  the  supracondyloid  foramen,  through  which  the  median 
nerve  and  brachial  artery  pass. 


THE   CONNECTIVE   TISSUES   AND   THE   SKELETAL  SYSTEM.  217 

THE  CARPAL  BONES. — Occasionally  an  os  centrale  is  present  in  addition  to 
the  usual  carpal  bones.  It  is  situated  on  the  dorsal  side  of  the  wrist  between  the 
navicular,  capitate  and  small  multangulum.  In  the  embryo  an  additional  piece 
of  cartilage  is  of  constant  occurrence  in  this  location,  but  usually  disappears 
during  later  development;  in  cases  where  it  persists,  ossification  takes  place 
to  form  the  os  centrale.  In  some  of  the  apes  the  os  centrale  is  of  constant 
occurrence  in  the  adult. 

THE  FEMUR. — The  gluteal  tuberosity  (ridge)  sometimes  projects  like  a 
comb,  forming  the  so-called  third  trochanter,  a  structure  homologous  with  the 
third  trochanter  in  the  horse  and  some  other  mammals. 

THE  TARSAL  BONES. — Cases  have  been  recorded  in  which  the  total  number 
of  tarsal  bones  was  reduced,  owing  to  congenital  synosteosis  (fusion)  of  the 
calcaneus  (os  calcis)  and  scaphoid  (navicular),  of  the  talus  (astragalus)  and 
calcaneus,  or  of  the  talus  and  scaphoid.  Occasionally  an  additional  bone — the 
trigonum — is  present  at  the  back  of  the  talus.  In  the  embryo,  the  talus  ossifies 
from  two  centers  which  normally  fuse  at  an  early  stage  into  a  single  center. 
The  trigonum  probably  represents  a  bone  produced  by  one  of  the  centers  which 
has  remained  separate. 

POLYDACTYLY. — This  anomaly  consists  of  an  increase  in  the  number  of 
fingers  or  toes,  or  both.  Any  degree  of  variation  may  exist  from  a  supernum- 
erary finger  or  toe  to  a  double  complement  of  fingers  or  toes.  The  causes  under- 
lying the  origin  of  such  anomalies  are  not  clear.  Some  assign  the  supernumer- 
ary digits  to  the  category  of  pathological  growths  or  neoplasms,  linking  them 
with  partial  duplicate  formations.  Others  explain  the  extra  digits  on  the  ground 
of  atavism  or  reversion  to  an  ancestral  type.  The  latter  explanation  assumes 
an  ancestral  type  with  more  than  five  digits.  But  neither  zoology  nor  paleon- 
tology has  found  any  vertebrate  form,  above  the  Fishes,  which  normally  pos- 
sesses more  than  five  digits  on  each  extremity.  Consequently  one  must  refer  to 
the  Fishes  for  some  ancestral  type  to  explain  the  existence  of  more  than  five 
digits.  Going  back  so  far  in  phylogenetic  history,  no  certainty  whatever  can  be 
attached  to  the  origin  of  supernumerary  digits,  for  it  is  not  even  known  from 
what  fins  the  extremities  of  the  higher  forms  are  derived.  Still  another  view 
regarding  the  origin  of  supernumerary  digits  is  that  they  are  due  to  certain  ex- 
ternal influences  among  which  the  most  important  is  the  mechanical  impression 
of  amniotic  folds  or  bands.  This,  however,  could  not  be  the  sole  cause  of 
polydactylism,  since  such  malformations  are  common  in  amphibian  embryos 
where  no  amnion  is  present. 

PRACTICAL  SUGGESTIONS. 

Embryonic  Connective  Tissue. — The  most  easily  obtained  material  for  the  study  of  the 
development  of  embryonic  connective  tissue  is  the  chick  embryo.  From  about  the  beginning 
of  the  second  day  to  the  end  of  the  third  day  of  incubation,  the  differentiation  of  the  meso- 


218  TEXT-BOOK  OF  EMBRYOLOGY. 

dermal  cells,  the  formation  of  the  primitive  segments,  and  the  further  differentiation  of  the 
primitive  segments  into  sclerotomes  and  myotomes  may  be  studied  in  successive  stages. 

The  embryos  are  removed  from  the  egg,  fixed  in  Flemming's  fluid  or  Zenker's 
fluid,  sectioned  transversely  in  paraffin,  stained  with  Heidenhain's  haematoxylin  and 
mounted  in  xylol  damar  (see  Appendix).  A  counterstain  with  a  weak  solution  of 
fuchsin  (0.5  per  cent,  in  distilled  water)  is  of  value  in  studying  the  fibers.  This  stain  is 
used  after  the  haematoxylin,  and  the  sections  are  then  rinsed  in  distilled  water  before  passing 
them  into  alcohol. 

Sections  of  the  umbilical  cord  of  any  mammalian  embryo,  prepared  by  the  above  technic, 
are  also  very  instructive. 

Primitive  Segments. — The  primitive  segments,  from  which  the  vertebrae,  etc.,  are  derived, 
can  be  studied  in  transverse  sections  of  chick  embryos  during  the  second  and  third  days  of 
incubation.  The  material  is  prepared  as  described  above  under  the  head  of  embryonic 
connective  tissue.  For  a  comprehensive  picture  of  the  series  of  primitive  segments,  sagittal 
sections  should  also  be  prepared. 

Blastemal  Stage  of  the  Skeletal  System. — Pig  embryos  of  12  to  14  mm.  are  fixed  in  Zenker's 
fluid  or  in  Bouin's  fluid,  cut  transversely  in  celloidin  or  paraffin,  stained  with  Weigert's 
haematoxylin  and  eosin,  and  mounted  in  xylol-damar  (see  Appendix).  The  anlagen  of  the 
vertebrae  appear  as  condensations  in  the  embryonic  connective  tissue.  Similar  condensa- 
tions in  the  extremities  indicate  the  anlagen  of  the  appendicular  skeleton,  and  in  the  region 
of  the  base  of  the  skull  the  anlage  of  the  chondrocranium. 

By  the  use  of  serial  sections,  and  the  method  of  plastic  reconstruction,  models  of  the 
anlagen  of  the  bones  may  be  made.  (For  method  of  reconstruction,  see  p.  638.) 

Cartilaginous  Stage  of  the  Skeletal  System. — Pig  embryos  of  about  35  mm.,  prepared  as  de- 
scribed above  under  the  head  of  the  Blastemal  Stage,  show  the  cartilaginous  elements  which 
precede  true  bone  in  the  vertebrae,  ribs,  base  of  the  skull,  and  certain  portions  of  the  appen- 
dicular skeleton.  In  order  to  get  a  comprehensive  idea  of  the  relation  of  the  cartilaginous 
elements  to  one  another,  it  is  often  necessary  to  make  models  of  parts  or  of  the  whole  of  the 
cartilaginous  skeleton  by  the  method  of  plastic  reconstruction  (p.  638).  Serial  sections  are 
of  course  necessary  for  this. 

Stage  of  Ossification,  (a)  Intramembranous  Bone. — Small  pieces,  including  the  skin  and 
dura  mater,  are  removed  from  the  skull  cap  of  a  four-month  human  foetus  or  of  a  four -inch 
pig  embryo,  fixed  in  Orth's  fluid,  hardened  for  several  days  in  alcohol,  decalcified  in  i  per 
cent,  hydrochloric  acid  (several  days),  washed  in  running  water  to  remove  the  acid,  sectioned 
at  right  angles  to  the  surface  in  celloidin  or  paraffin,  stained  with  Weigert's  haematoxylin 
and  picro-acid-fuchsin,  and  mounted  in  xylol-damar. 

(b)  Intracartilaginous  and  Subperiosteal  Bone. — Remove  the  forearms  and  legs  of  fcetal  pigs 
of  five  to  six  inches,  and  prepare  by  the  technic  given  in  the  preceding  paragraph,  cutting  the 
sections  parallel  to  the  long  axes  of  the  developing  bones. 

In  preparing  specimens  for  the  study  of  either  intramembranous  or  intracartilaginous  de- 
velopment, both  fixation  and  decalcification  can  be  done  at  the  same  time.  Put  the  fresh 
material  in  Bouin's  picro-formalin-acetic  mixture  and  let  it  remain  for  a  week,  with 
one  or  two  changes  of  the  fluid;  then  wash  in  several  changes  of  alcohol  (40  to  50  per  cent.). 
A  few  drops  of  ammonia  added  to  the  alcohol  facilitates  the  removal  of  the  picric  acid. 
Further  treatment  is  the  same  as  after  any  ordinary  fixation.  The  results  are  good. 

The  earlier  stages  in  the  ossification  of  the  vertebrae  and  the  base  of  the  skull  can  be  studied 
in  pig  embryos  of  40  to  50  mm.  The  embryos  are  fixed,  and  at  the  same  time  decalci- 
fied (see  preceding  paragraph),  in  Bouin's  fluid.  They  are  sectioned  transversely  in 


THE   CONNECTIVE  TISSUES   AND   THE   SKELETAL   SYSTEM.  219 

celloidin,  stained  with  Weigert's  haematoxylin  and  eosin  and  mounted  in  xylol-damar 
(see  Appendix). 

Ossification  of  the  vault  of  the  skull  can  be  studied  in  pig  embryos  of  40  mm.  and  longer 
by  means  of  the  technic  described  under  Intramembranous  Bone  (p.  218). 

Ossification  of  the  appendicular  skeleton  can  be  studied  in  the  extremities  of  pig  embryos 
of  three  inches  and  longer,  by  means  of  the  technic  for  Intracartilaginous  Bone  (p.  218). 

Models  of  parts  or  of  the  whole  of  the  osseous  skeleton  can  be  made  by  the  method  of 
plastic  reconstruction.  For  this,  of  course,  serial  sections  are  necessary  (see  p.  638). 

Transparent  Preparations. — A  method  which  renders  the  tissues  more  or  less  transparent 
and  differentiates  the  bone  is  extremely  useful  in  studying  the  development  of  the  osseous 
skeleton.  Embryos  of  any  kind  are  put  into  strong  alcohol  and  left  indefinitely — the  longer 
the  better.  They  become  much  shrunken,  but  that  is  not  injurious.  They  are  then  put  into 
a  3  per  cent,  aqueous  solution  of  potassium  hydrate  (KOH).  If  the  solution  becomes  colored 
by  the  pigment  from  the  blood  it  should  be  changed  as  often  as  necessary.  The  embryos 
become  quite  transparent  in  a  short  time,  a  few  days  or  more,  depending  upon  their  size. 
They  are  then  put  carefully  into  equal  parts  of  glycerin  and  water  for  a  day  or  two,  then  into 
stronger  glycerin,  and  finally  preserved  in  pure  glycerin.  The  tissues,  except  bone,  are 
quite  transparent;  the  bone  remains  white,  and  the  entire  osseous  skeletal  system,  so  far  as 
it  is  developed  at  any  particular  stage,  can  be  seen  clearly. 

For  technic  to  demonstrate  the  growth  of  bones,  see  small  print  in  the  text,  page  180. 

Fat. — Fix  bits  of  tissue  from  the  axilla  and  groin  of  a  five-  or  six-inch  foetal  pig  in  i  per 
cent,  osmic  acid  for  twenty-four  hours.  Wash  in  running  water  for  several  hours  and 
preserve  in  pure  glycerin.  Tease  small  pieces  of  tissue  on  a  slide  and  mount  in  glycerin. 

References  for  Further  Study. 

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BADE,  P.:  Die  Entwickelung  des  menschlichen  Skeletts  bis  zur  Geburt.  Arch.  j.  mik. 
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BARDEEN,  C.  R.:  Numerical  Vertebral  Variations  in  the  Human  Adult  and  Embryo. 
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BARDEEN,  C.  R.:  Studies  of  the  Development  of  the  Human  Skeleton.  American 
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BARTELS,  M.:  Ueber  Menschenschwanze.     Arch.  j.  Anthropol.,  Bd.  XII. 

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In  Hertwig's  Handbuch  der  vergleich.  u.  experiment.  Entwickelungslehre  der  Wirbeltiere, 
Bd.  Ill,  Teil  II,  1905. 

SPULER,  A.:  Beitrage  zur  Histologie  und  Histogenese  der  Binde-und  Stiitzsubstanz. 
Anat.  Hejte,  Heft  XXI,  1896. 

THILENIUS,  G.:  Untersuchungen  iiber  die  morphologische  Bedeutung  accessorischer 
Elemente  am  menschlichen  Carpus  (und  Tarsus).  Morph.  Arbeiten,  Bd.  V,  1896. 

THOMSON,  A.:  The  Sexual  Differences  of  the  Foetal  Pelvis.  Jour,  of  Anat.  and  PhysioL, 
Vol.  XXXIII,  1899. 

TORNIER,  G.:  Das  Entstehen  der  GelenWermen.  Arch.  f.  Entw.-Mechanik,  Bd.  I, 
1895. 

WALDEYER,  W.:  Kittsubstanz  und  Grundsubstanz,  Epithel  und  Endothel.  Arch.  }. 
inik.  Anat.,  Bd.  LVII,  1900. 

WEISS,  A. :  Die  Entwickelung  der  Wirbelsaule  der  weissen  Ratte,  besonders  der  vorder- 
sten  Halswirbel.  Zeitschr.  /.  wissensch.  Zool.,  Bd.  LXIX,  1901. 

ZIMMERMANN,  K.:  Ueber  Kopfhohlenrudimente  beim  Menschen.  Arch.  /.  mik.  Anat., 
Bd.  LIII,  1899. 


CHAPTER  X. 

THE  DEVELOPMENT  OF  THE  VASCULAR  SYSTEM. 
THE  BLOOD  VESSELS  AND  BLOOD. 

Inasmuch  as  the  blood  vessels  form  such  an  extensive  and  extremely  com- 
plicated system,  it  would  be  obviously  beyond  the  scope  of  this  book  to  con- 
sider the  details  of  the  development  of  all  parts  of  this  system.  A  somewhat 
detailed  discussion  of  the  heart  and  of  the  larger  vascular  trunks  will  be  given 
but  in  the  case  of  the  smaller  vessels  very  brief  statements  must  suffice. 

The  Heart. 

Despite  the  fact  that  in  the  adult  the  heart  is  so  intimately  associated  with 
the  blood  vessels  and  blood,  it  begins  to  develop  quite  independently,  and  is 
said  to  begin  to  beat  before  the  vessels  containing  the  blood  are  connected  with 
it.  It  is  one  of  the  first  organs  to  appear,  and  at  a  very  early  stage  assumes  the 
function  which  it  maintains  throughout  the  life  of  the  organism.  The  primitive 
heart  is  a  very  simple  structure,  consisting  merely  of  a  tube  whose  wall  is 
capable  of  contractile  activity.  One  end  of  this  tube  is  attached  to  the  arterial 
system  and  the  other  to  the  venous  system.  This  simple  form  is  elaborated 
more  and  more  during  development  until  it  reaches  the  complicated  structure 
characteristic  of  the  adult. 

The  heart  has  a  peculiar  origin  in  that  it  arises  as  two  separate  parts  or 
anlagen  which  unite  secondarily.  In  the  chick,  for  example,  it  appears  during 
the  first  day  of  incubation,  at  a  time  when  the  germ  layers  are  still  flat.  The 
ccelom  in  the  cephalic  region  becomes  dilated  to  form  the  so-called  primitive 
pericardial  cavity  (parietal  cavity),  and  at  the  same  time  a  space  appears  on 
each  side,  not  far  from  the  medial  line,  in  the  mesodermal  layer  of  the  splanchno- 
pleure  (Fig.  194).  These  spaces  at  first  are  filled  with  a  gelatinous  substance  in 
which  lie  a  few  isolated  cells.  These  cells  then  take  on  the  appearance  of  en- 
dothelium  and  line  the  cavities,  and  the  mesothelium  in  this  vicinity  is  changed 
into  a  distinct,  thickened  layer  of  cells.  Now  by  a  bending  ventrally  of  the 
splanchnopleure  the  cavities  or  vessels  are  carried  toward  the  midventral  line 
(Fig.  194).  The  bending  continues  until  the  entoderm  of  each  side  meets  and 
fuses  with  that  of  the  opposite  side,  thus  closing  in  a  flat  cavity — the  fore-gut. 
The  entoderm  ventral  to  the  cavity  breaks  away  and  allows  the  medial  walls 
of  the  two  endothelial  tubes  to  come  in  contact.  These  walls  then  break  away 
and  the  tubes  are  united  in  the  midventral  line  to  form  a  single  tube  (Fig.  194), 

222 


THE   DEVELOPMENT   OF  THE   VASCULAR  SYSTEM. 


223 


which  extends  longitudinally  for  some  distance  in  the  cervical  region  of  the 
embryo.  The  mesothelial  layers  of  opposite  sides  meet  dorsal  and  ventral 
to  the  endothelial  tube,  forming  the  dorsal  and  ventral  mesocardium  (Fig.  194). 
In  the  meantime  the  cephalic  end  of  the  tube  has  united  with  the  arterial  system, 


Ttjaryq* 
J)ors.  njesoca.rd.ium 


Myocardium 
MesotfjeUury) 


pericurd. 
Cavity 

^-^^•^ 

^^^sLrf 

£^0ca/-^*V/7 
(E  ydotfyeLi  ury) 

FIG.  194. — Diagrams  showing  the  two  anlagen  of  the  heart  and  their  union  to  form  a  single 
structure;  made  from  camera  lucida  tracings  of  transverse  sections  of  chick  embryos.  In  C 
the  ventral  mesocardium  has  disappeared  (see  text). 

and  the  caudal  end  with  the  venous  system;  and  in  a  short  time  the  dorsal  and 
ventral  mesocardia  disappear  and  leave  the  heart  suspended  by  its  two  ends  in 
the  primitive  pericardial  cavity.  The  conditions  at  this  point  may  be  sum- 
marized thus :  The  heart  is  a  double- walled  tube — the  inner  wall  composed  of 


224 


TEXT-BOOK  OF  EMBRYOLOGY. 


endothelium  and  destined  to  become  the  endocardium,  the  outer  wall  of  a 
thicker  mesothelial  layer  and  destined  to  become  the  myocardium — the  two  walls 
separated  by  a  considerable  space.  The  organ  hangs,  as  it  were,  in  the  primi- 
tive pericardial  cavity  (ccelom) ,  connected  at  its  cephalic  end  with  the  ventral 
aortic  trunk  and  at  its  caudal  end  with  the  omphalomesenteric  veins. 

In  all  Mammals  thus  far  studied  the  principle  of  development  in  the  earlier 
stages  is  essentially  the  same  as  in  the  chick.  The  double  origin  of  the  heart  is 
even  more  marked  because  of  the  relatively  late  closure  of  the  fore-gut.  There 
are  no  observations  on  the  origin  of  the  heart  in  human  embryos,  but  it  is 


Dorsal  aortic  root 


Gut  (pharynx) 


.Dorsal 
mesocardium 


•Pericardial 
cavity  (ccelom) 

Endocardium 
(endothelium) 


Myocardium 


FIG.  195. — Transverse  section  of  a  human  embryo  of  2.69  mm.     von  Spee,  Kollmann's  Atlas. 


reasonable  to  assume  that  it  has  the  same  double  origin  as  in  other  Mammals, 
although  in  embryos  of  2  to  3  mm.  the  organ  has  already  become  a  single  tube 
(Figs.  195  and  196).  At  this  stage  the  tube  is  somewhat  coiled. 

The  origin  of  the  endothelium  of  the  heart  (endocardium)  is  not  known  with 
certainty.  Some  investigators  in  their  researches  among  the  lower  Vertebrates 
have  suggested  that  it  is  derived  primarily  from  the  entoderm ;  others  have  sug- 
gested a  possible  derivation  from  both  entoderm  and  mesoderm;  still  others  hold 
that  it  is  derived  from  the  mesenchyme  (mesoderm) .  It  seems  to  be  undis- 
puted, however,  that  the  muscular  wall  of  the  heart  (myocardium)  is  a  derivative 
of  the  mesothelium  (mesoderm). 


THE  DEVELOPMENT  OF  THE  VASCULAR   SYSTEM. 


225 


While  the  double  origin  of  the  heart  is  characteristic  of  all  amniotic  Vertebrates  (Reptiles, 
Birds,  Mammals),  in  all  the  lower  forms  the  organ  arises  as  a  single  anlage.  In  the  region 
of  the  fore-gut  the  two  halves  of  the  ccelom  are  separated  by  a  ventral  mesentery  which 
extends  from  the  gut  to  the  ventral  body  wall,  and  which  is  composed  of  two  layers  of  mesothe- 
lium  with  a  small  amount  of  mesenchyme  between  them.  In  the  mesenchyme  a  cavity 


Oral  fossa 


Ventral  aortic 
trunk 


Ventricle< • 


Ant.  cardinal  vein 
Duct  of  Cuvier 
Umbilical  vein 


Ventricle 

Atrium 

Diaphragm 

Duct  of  Cuvier 

Liver 

Duct  of  liver 


FIG.  196. — Ventral  view  of  reconstruction  of  human  embryo  of  2.15  mm.     His. 

The  ventral  body  wall  has  been  removed.     The  vessels  (in  black)  at  the  sides  of  the  duct 

of  the  liver  are  the  omphalomesenteric  veins. 

appears  and  is  lined  by  a  single  layer  of  flat  (endothelial)  cells.  This  cavity  extends  longi- 
tudinally for  some  distance  in  the  cervical  region  and  with  its  endothelial  and  mesothelial 
walls  constitutes  the  simple  cylindrical  heart.  On  the  dorsal  side  it  is  connected  with  the 
gut  by  a  portion  of  the  mesentery  which  is  called  the  dorsal  mesocardium;  on  the  ventral 
side  it  is  connected  with  the  ventral  body  wall  by  the  ventral  mesocardium  (Fig.  197).  Thus 


Entoderm 
Mesoderm  (visceral) 

Dorsal  mesocardium 


Heart 

Pericard.  cavity 
(coelom) 


Endothelium 
Mesoderm  (parietal) 
Ventral  mesocardium 
Ectoderm 


FIG.  197. — Ventral  part  of  transverse  section  through  the  heart  region  of  Salamandra 
maculosa  embryo  with  4  branchial  arches.     Rabl. 

the  heart  is  primarily  a  single  structure.  The  difference  between  the  two  types  of  develop- 
ment is  not  a  fundamental  one  but  simply  depends  upon  the  difference  in  the  germ  layers. 
In  the  lower  forms  the  germ  layers  are  closed  in  ventrally  from  the  beginning,  and  the  heart 
appears  in  a  medial  position.  In  the  higher  forms  the  germ  layers  for  a  time  remain  spread 
out  upon  the  surface  of  the  yolk  or  yolk  sac,  and  the  heart  begins  to  develop  before  they 
close  in  on  the  ventral  side  of  the  embryo.  Consequently  the  heart  arises  in  two  parts  which 
are  carried  ventrally  by  the  germ  layers  and  unite  secondarily. 


226  TEXT-BOOK  OF  EMBRYOLOGY. 

The  further  development  of  the  heart  consists  of  various  changes  in  the 
shape  of  the  tube  and  in  the  structure  of  its  walls.  At  the  same  time  the  dila- 
tation of  the  ccelom  (primitive  pericardial  cavity)  in  the  cervical  region  is  of  im- 
portance in  affording  room  for  the  heart  to  grow.  In  the  chick,  for  example, 
the  tube  begins,  toward  the  end  of  the  first  day  of  incubation,  to  bend  to  the 
right;  during  the  second  day  it  continues  to  bend  and  assumes  an  irregular 
S-shape.  This  bending  process  has  not  been  observed  in  human  embryos,  but 
other  Mammals  show  the  same  process  as  the  chick.  In  a  human  embryo  of 
2.15  mm.  the  S-shaped  heart  is  present  (Fig.  196).  The  venous  end,  into 
which  the  omphalomesenteric  veins  open,  is  situated  somewhat  to  the  left,  ex- 
tends cranially  a  short  distance  and  then  passes  over  into  the  ventricular  portion. 
The  latter  turns  ventrally  and  extends  obliquely  across  to  the  right  side,  then 
bends  dorsally  and  cranially  to  join  the  aortic  bulb  which  in  turn  joins  the 
ventral  aortic  trunk  in  the  medial  line.  The  endothelial  tube,  which  is  still 
separated  from  the  muscular  wall  by  a  considerable  space,  becomes  somewhat 


Vent,  aortic  trunk 


FIG.  198. — Ventral  view  heart  of  human  embryo  of  4.2  mm.     His. 
The  atria  are  hidden  behind  the  ventricular  portion. 

constricted  at  its  junction  with  the  aortic  bulb  to  form  the  so-called  /return 
Halleri.  During  these  changes  the  heart  as  a  whole  increases  in  diameter, 
especially  the  ventricular  portion.  Gradually  the  venous  end  of  the  heart 
moves  cranially  and  in  embryos  of  4.2  mm.  lies  in  the  same  transverse  plane  as 
the  ventricular  portion.  The  latter  lies  transversely  across  the  body  (Fig.  198). 
At  the  sa*ne  time  two  evaginations  appear  on  the  venous  end,  which  repre- 
sent the  anlagen  of  the  atria.  In  embryos  of  about  5  mm.  further  changes 
have  occurred,  which  are  represented  in  Fig.  199.  The  two  atrial  anlagen  are 
larger  than  in  the  preceding  stage  and  surround,  to  a  certain  extent,  the  proxi- 
mal end  of  the  aortic  trunk.  As  they  enlarge  still  more  in  later  stages,  they  come 
in  contact,  their  medial  walls  almost  entirely  disappear,  and  they  form  a  single 
chamber.  The  ventricular  portion  of  the  heart  becomes  separated  into  a  right 
and  a  left  part  by  the  interventricular  furrow  (Fig.  199) ;  the  right  part  is  the 
anlage  of  the  right  ventricle,  the  left  part,  of  the  left  ventricle.  At  the  same  time 
the  atrial  portion  has  moved  still  farther  cranially  so  that  it  lies  to  the  cranial 


THE   DEVELOPMENT   OF  THE  VASCULAR   SYSTEM.  227 

side  of  the  ventricular  portion.  The  venous  and  arterial  ends  of  the  heart  have 
thus  reversed  their  original  relative  positions.  At  this  point  it  should  be 
noted  that  the  atrial  end  of  the  heart  is  connected  with  the  large  venous  trunk 
formed  by  the  union  of  the  omphalomesenteric  veins  and  the  ducts  of  Cuvier — 
the  sinus  venosus. 

During  the  changes  in  the  heart  as  a  whole,  certain  changes  also  occur  in  the 
endothelial  and  muscular  walls.  The  walls  of  the  atria  are  composed  of  com- 
pact plates  of  muscle  with  the  endothelium  closely  investing  the  inner  surface. 
The  walls  of  the  ventricular  portion,  on  the  other  hand,  become  thicker  and  are 
composed  of  an  outer  compact  layer  of  muscle  and  an  inner  layer  made  up  of 


Right  atrium  il  ^  ISk  Left  atrium 


Right  ventricle    f  '  ^M  •  Left  ventricle 


Interventricular  furrow 
FIG.  199. — Ventral  view  of  heart  of  human  embryo  of  5  mm.     His. 

% 

trabeculae  which  are  closely  invested  by  the  endothelium.  Everywhere  the 
endothelium  is  closely  applied  to  the  inner  surface  of  the  myocardium,  the  space 
which  originally  existed  between  the  endothelium  and  mesothelium  being 
obliterated. 

The  embryonic  heart  in  Mammals  in  the  earlier  stages  resembles  that  of  the  adult  in  the 
lower  Vertebrates  (Fishes).  The  atrial  portion  receives  the  blood  from  the  body  veins  and 
conveys  it  to  the  ventricular  portion  which  in  turn  sends  it  out  through  the  arteries  to  the 
body.  The  circulation  is  a  single  one.  This  condition  changes  during  the  fcetal  life  of 
Mammals  with  the  development  of  the  lungs.  The  same  transition  occurs  in  the  ascending 
scale  of  development  in  the  vertebrate  series  in  those  forms  in  which  gill  breathing  is  replaced 
by  lung  breathing.  The  change  consists  of  a  division  of  the  heart  and  circulation,  so  that  the 
single  circulation  becomes  a  double  circulation.  In  other  words,  the  heart  is  so  divided  that 
the  lung  (pulmonary)  circulation  is  separated  from  the  general  circulation  of  the  body.  This 
division  first  appears  in  the  Dipnoi  (Lung  Fishes)  and  Amphibians  in  which  gill  breathing 
stops  and  lung  breathing  begins,  although  here  the  division  is  not  complete.  In  Reptiles 
the  division  is  complete  except  for  a  small  direct  communication  between  the  ventricles 


228 


TEXT-BOOK  OF  EMBRYOLOGY. 


Fig.  200  represents  the  dorsal  half  of  the  heart  at  a  stage  when  all  the 
chambers  are  in  open  communication,  and  shows  the  conditions  in  a  single  cir- 
culation but  with  the  beginning  of  a  separation.  The  atria  are  rather  thin- 
walled  chambers,  the  ventricles  have  relatively  thick  walls.  Between  the 


Septum  spurium 

Atrial  septum 
(septum  superius) 

Opening  of  sinus  venosus 


Right  atrium 
Left  atrium 
Atrio-ventricular  canal 


Right  ventricle 
Ventricular  septum 
Left  ventricle 


FIG.  200. — Dorsal  half  of  heart  (seen  from  ventral  side)  of  a  human  embryo  of  10  mm.     His. 

atrial  and  ventricular  portions  is  a  canal — the  atria-ventricular  canal — which 
affords  a  free  passage  for  the  blood.  From  the  cephalic  side  of  the  atrial  por- 
tion a  ridge  projects  into  the  cavity.  This  ridge  represents  a  remnant  of  the 
original  medial  walls  of  the  two  atria  and  marks  the  beginning  of  the  future 


Septum  superius 

Sinus  venosus 

Valvulae  venosae . 

Right  atrium   »'-J 

Right  ventricle _ 

|    | 
Ventricular  septum B 


Foramen  ovale 
Atrial  septum 
; —   Left  atrium 

Atrio-ventricular  valves 


.  Atrio-ventricular  canals 
Left  ventricle 


FIG.  201. — Dorsal  half  of  heart  showing  chambers  and  septa.     (Semidiagrammatic.) 

Modified  from  Born. 

atrial  septum.'  The  opening  of  the  sinus  venosus  is  seen  on  the  dorsal  wall  of  the 
right  atrium.  Primarily  both  atria  communicated  directly  with  the  simis 
venosus,  but  in  the  course  of  development  the  opening  of  the  latter  migrated  to 
the  right  and  at  this  stage  is  found  in  the'  wrall  of  the  right  atrium.  The  opening 


THE   DEVELOPMENT  OF  THE  VASCULAR  SYSTEM. 


229 


is  guarded,  as  it  were,  by  a  lateral  and  a  medial  fold  the  significance  of  which  will 
be  described  later.  The  ventricular  portion  also  shows  a  ridge  projecting  from 
the  caudal  side,  which  corresponds  to  the  interventricular  groove  and  represents 
the  beginning  of  the  ventricular  septum. 

The  Septa. — The  further  changes  are  largely  concerned  with  the  separation 
of  the  heart  into  right  and  left  sides,  and  with  the  development  of  the  valves. 
The  atria  become  separated  by  the  further  growth  on  the  cephalic  side,  of  the 
ridge  which  has  already  been  mentioned  and  which  is  known  as  the  septum 
superius  (Figs.  200  and  201).  This  septum  grows  across  the  cavity  of  the  atria 
until  it  almost  reaches  the  atrio- ventricular  canal,  forming  the  septum  atriorum. 
A  portion  of  the  septum  then  breaks  away,  leaving  the  two  atria  still  in  corn- 


sinus  venosus 


Left  valvula  venosa 


Right  valvula  venosa 


Right  ventricle 


Right  atrio- .. 

ventricular  canal 


Right  ventricle 


Atrial  septum 

Pulmonary  vein 


Left  atrium 


Left  atrio- 
ventricular  canal 


Left  ventricle 


Interventricular  furrow  Ventricular  septum 

FIG.  202. — Dorsal  half  of  heart  (ventral  view)  of  rabbit  embryo  of  5.8  mm.     Born. 

munication.  This  secondary  opening  is  the  foramen  ovate  which  persists 
throughout  foetal  life  but  closes  soon  after  birth.  The  atrio-ventricular  canal 
also  becomes  divided  into  two  passages  by  a  ridge  from  the  dorsal  wall  and 
one  from  the  ventral  wall  uniting  with  each  other  and  finally  with  the  septum 
atriorum  (Fig.  201).  Thus  the  two  atria  would  be  completely  separated  if  it 
were  not  for  the  foramen  ovale. 

During  the  separation  of  the  atria,  a  division  of  the  ventricular  portion  of  the 
heart  also  occurs.  On  the  caudal  side  of  the  ventricular  portion  a  septum  ap- 
pears and  gradually  grows  across  the  cavity  forming  the  septum  ventriculorum 
(Figs.  200  and  201).  This  septum  is  situated  nearer  the  right  side  and  is  in- 
dicated on  the  outer  surface  by  a  groove  which  becomes  the  sulcus  longitudinalis 


230 


TEXT-BOOK  OF  EMBRYOLOGY. 


anterior  and  posterior.     The  dorsal  edge  of  this  septum  finally  fuses  with  the 
septum  dividing  the  atrio-ventricular  canal,  but  for  a  time  its  ventral  edge  re- 
mains free,  leaving  an  opening  between  the  two  ventricles  (Figs.  202  and  203). 
This  opening  then  becomes  closed  in  connection  with  the  division  of  the 


Aorta  «• 


Aortic  septum 


Interventricular  opening £L 


Right  atrio-ventricu- 
lar orifice  ~ 


Right  ventricle  ~-ff 
Ventricular  septum 


Pulmonary  artery 


Left  atrio-ventricular  orifice 
-  Left  ventricle 


FIG.  203. — Ventricles  and  proximal  ends  of  aorta  and  pulmonary  artery  of  a  7.5  mm.  human 
embryo.     Lower  walls  of  ventricles  have  been  removed.     Kollmann's  Atlas. 

aortic  bulb  and  ventral  aortic  trunk.  On  the  inner  surface  of  the  aortic  trunk, 
at  a  point  where  the  branches  which  form  the  pulmonary  arteries  arise,  two 
ridges  appear,  grow  across  the  lumen  and  fuse  with  each  other,  thus  dividing 
the  vessel  into  two  channels.  This  partition — the  septum  aorticum  (Fig.  204)— 
gradually  grows  toward  the  heart  through  the  aortic  bulb  and  finally  unites  with 


FIG.  204. — Diagrams  representing  the  division  of  the  ventral  aortic  trunk  into  aorta  and 
pulmonary  artery  and  the  development  of  the  semilunar  valves.     Hochstetter. 

the  ventral  edge  of  the  ventricular  septum,  thus  closing  the  opening  between  the 
two  ventricles.  Corresponding  with  the  edges  of  the  septum  aorticum,  a  groove 
appears  on  each  side  of  the  aortic  trunk  and  gradually  grows  deeper  and  ex- 
tends toward  the  heart,  until  finally  the  trunk  and  aortic  bulb  are  split  longitudi- 


THE   DEVELOPMENT  OF  THE  VASCULAR   SYSTEM.  231 

nally  into  two  distinct  vessels,  one  of  which  is  connected  with  the  right  ventricle 
and  becomes  the  pulmonary  artery,  the  other  with  the  left  ventricle  and  becomes 
the  proximal  part  of  the  aortic  arch  (Fig.  203) .  The  result  of  the  formation  of 
these  various  septa  is  the  division  of  the  entire  heart  into  two  sides.  The 
atrium  and  ventricle  of  each  side  are  in  communication  through  the  atrio- 
ventricular  foramen,  the  two  sides  are  in  communication  only  by  the  fora- 
men ovale  which  is  but  a  temporary  opening. 

After  the  opening  of  the  sinus  venosus  is  shifted  to  the  right  atrium,  the  left 
atrium  for  a  short  period  has  no  vessels  opening  into  it.  As  soon,  however,  as 
the  pulmonary  veins  develop,  they  form  a  permanent  union  with  the  left  atrium 
(Fig.  202).  At  first  two  veins  arise  from  each  lung,  which  unite  to  form  a  single 
vessel  on  each  side;  the  two  single  vessels  then  unite  to  form  a  common  trunk 
which  opens  into  the  left  atrium  on  the  cephalic  side.  As  development  pro- 
ceeds, the  wall  of  the  single  trunk  is  gradually  absorbed  in  the  wall  of  the  atrium, 
until  the  single  vessel  from  each  side  opens  separately.  Absorption  continu- 
ing, all  four  veins,  two  from  each  lung  finally  open  separately.  This  is  the  con- 
dition usually  found  in  the  adult.  A  partial  failure  in  the  absorption  may  leave 
one,  two,  or  three  vessels  opening  into  the  atrium.  Such  variations  are  not 
infrequently  met  with  in  the  pulmonary  veins. 

The  Valves.— If  all  the  passageways  between  the  different  chambers  of 
the  heart  and  the  large  vascular  trunks  were  to  remain  free  and  clear,  there 
would  be  nothing  to  prevent  the  blood  from  flowing  contrary  to  its  proper  course. 
Consequently  five  sets  of  valves  develop  in  relation  to  these  orifices,  and  are  so 
arranged  that  they  direct  the  blood  in  a  certain  definite  direction.  These  ap- 
pear (a)  at  the  openings  of  the  large  venous  trunks  into  the  right  atrium,  (b)  at 
the  opening  between  the  right  atrium  and  right  ventricle,  (c)  at  the  opening 
between  the  left  atrium  and  left  ventricle,  (d)  at  the  opening  between  right 
ventricle  and  pulmonary  artery  and  (e)  at  the  opening  between  the  left  ven- 
tricle and  aorta.  No  valves  develop  at  the  openings  of  the  pulmonary  veins 
into  the  left  atrium. 

(a)  The  sinus  venosus  (which  is  formed  by  the  union  of  the  large  body  veins) 
opens  into  the  right  atrium  on  its  cranial  side,  as  has  already  been  mentioned 
(p.  228).  By  a  process  of  absorption,  similar  to  that  in  the  case  of  the  pul- 
monary veins,  the  wall  of  the  sinus  is  taken  up  into  the  wall  of  the  atrium.  The 
result  is  that  the  vena  cava  superior,  vena  cava  inferior,  and  sinus  coronarius 
(a  remnant  of  the  left  duct  of  Cuvier)  open  separately  into  the  atrium.  As  the 
sinus  is  absorbed,  its  wall  forms  two  ridges  on  the  inner  surface  of  the  atrium, 
one  situated  at  the  right  of  the  opening  and  one  at  the  left  (Figs.  201  and  202). 
These  two  ridges — valvula  venoscB — are  united  at  their  cranial  ends  with  the 
septum  spurium  (Fig.  200),  a  ridge  projecting  from  the  cephalic  wall  of  the 
atrium.  The  septum  spurium  probably  has  a  tendency  to  draw  the  two  valves 


232  TEXT-BOOK  OF  EMBRYOLOGY. 

together  and  prevent  the  blood  from  flowing  back  into  the  veins.  The  left 
valve  and  the  septum  spurium  later  atrophy  to  a  certain  extent  and  probably 
unite  with  the  septum  atriorum  to  form  part  of  the  limbus  fossa  ovalis  (Vieus- 
senii).  The  right  valve  is  the  larger  and  in  addition  to  its  assistance  in  prevent- 
ing a  backward  flow  of  blood  into  the  veins,  it  also  serves  to  direct  the  flow  to- 
ward the  foramen  ovale.  As  the  veins  come  to  open  separately,  the  cephalic 
part  of  the  right  valve  disappears;  the  greater  part  of  the  remainder  becomes 
the  valvula  vence  cavtz  inferioris  (Eustachii)  and  during  fcetal  life  directs  the 
blood  toward  the  foramen  ovale.  In  the  adult  it  becomes  a  structure  of 
variable  size.  A  small  part  of  the  remainder  of  the  right  valve  forms  the  valvula 
sinus  coronarii  (Thebesii)  which  guards  the  opening  of  the  coronary  sinus. 

(b)  and  (c)  The  valves  between  the  atrium  and  ventricle  on  each  side 
develop  for  the  most  part  from  the  walls  of  the  triangular  atrio-ventricular 
opening  (ostium  atrio-ventriculare) .  Elevations  or  folds  appear  on  the  rims  of 
the  openings  and  project  into  the  cavities  of  the  ventricles  where  they  become 
attached  to  the  muscle  trabeculae  of  the  ventricle  walls  (Figs.  205  and  206). 
On  the  right  side  three  of  these  folds  appear,  and  develop  into  the  valvula 


Valve 


«      .,       ,.         .   .  •         flwiv^  JJK n         jwjRjfwun  p$fMti\  ira~ wi n  n/MuiAi         (-/nordse  tcnclincsE 

Cavity  of  ventricle      OTMM       MM$®  fflj\H       IFwl 

Trabeculae  carneas 

FIG.  205. — Diagrams  representing  the  development  of  the  atrio  ventricular  valves,  chordae 
tendinese,  and  papillary  muscles.     Gegenbaur. 

tricuspidalis  which  guards  the  right  atrio-ventricular  orifice.  On  the  left  side 
only  two  folds  appear,  and  these  become  the  valvula  biscuspidalis  (mitralis) 
which  guards  the  left  atrio-ventricular  orifice.  These  valves,  which  are  at  first 
muscular,  soon  change  into  dense  connective  tissue.  The  muscle  trabeculae  to 
which  they  are  attached  also  undergo  marked  changes.  Some  become  con- 
densed at  the  ends  which  are  attached  to  the  valves  into  slender  tendinous  cords 
— the  chordce  tendinece,  while  at  their  opposite  ends  they  remain  muscular  as  the 
Mm.  papillares;  others  remain  muscular  and  lie  in  transverse  planes  in  the 
ventricles,  or  fuse  with  the  more  compact  part  of  the  muscular  wall,  or  form 
irregular,  anastomosing  bands  and  constitute  the  trabecula  carnea  (Fig.  205). 
(d)  and  (e)  The  valves  of  the  pulmonary  artery  and  aorta  develop  at  the 
point  where  originally  the  endothelial  tube  was  constricted  to  form  the  fretum 
Halleri  (p.  226)  where  the  ventricular  portion  of  the  heart  joined  the  aortic 


THE  DEVELOPMENT   OF  THE   VASCULAR   SYSTEM. 


233 


bulb.  Before  the  aortic  trunk  and  bulb  are  divided  into  the  aortic  arch  and 
pulmonary  artery,  four  protuberances  appear  in  the  lumen  (Fig.  204).  The 
septum  aorticum  then  divides  the  two  which  are  opposite  so  that  each  vessel 
receives  three  (Fig.  204).  These  then  become  concave  on  the  side  away  from 
the  heart,  in  a  manner  which  has  not  been  fully  determined,  and  at  the  same 


Atrial  septum 

Right  atrium 

Right  atrio- 

ventricular 

(tricuspid)  valves 

Right  ventricle 


Ventricular 
septum 


Pericardial  cavity 


Dorsal  aortic  roots 


Amnion 


Upper  limb  bud 


Left  atrium 


Left  atrio- 
ventricular 
(bicuspid)  valves 


Left  ventricle 


FIG   206. — Transverse  section  of  pig  embryo  of  14  mm.     Photograph. 

time  enlarge  so  that  they  close  the  lumen.  Those  in  the  pulmonary  artery  are 
known  as  the  valvulce  semilunares  arteria  pulmonalis,  those  in  the  aorta  as  the 
valvulce  semilunares  aorta. 

Changes  after  Birth. — The  migratory  changes  of  the  heart  from  its  origi- 
nal position  in  the  cervical  region  to  its  final  position  in  the  thorax  will  be  con- 
sidered in  connection  with  the  development  of  the  pericardium  (Chap,  XIV). 
With  the  exception  of  the  septum  atriorum,  the  heart  acquires  during  foetal  life 
practically  the  form  and  structure  characteristic  of  the  adult  (Fig.  207) ,  So  long 


234 


TEXT-BOOK  OF  EMBRYOLOGY. 


as  the  individual  continues  to  grow,  the  heart,  generally  speaking,  increases  in  size 
accordingly.  This  increase  takes  place  by  intussusception  in  the  endocardium 
and  myocardium.  At  the  time  of  birth  the  two  atria  are  in  communication 
through  the  foramen  ovale  which  is  simply  an  orifice  in  the  atrial  septum  (Fig. 208) . 
Thus  the  blood  which  is  brought  to  the  right  atrium  by  the  body  veins  is  al- 
lowed to  pass  directly  into  the  left  atrium,  thence  to  the  left  ventricle,  and  thence 
is  forced  out  to  the  body  again  through  the  aorta.  A  certain  amount  of  blood 
also  passes  from  the  right  atrium  into  the  right  ventricle  and  thence  into  the 
pulmonary  artery;  but  this  blood  does  not  enter  the  lungs  but  passes  directly 
into  the  aorta  through  the  ductus  arteriosus  (Fig.  207) .  After  birth  the  lungs  begin 


Innominate  artery 

Branches  of  right 
pulmonary  artery 

Arch  of  aorta 

Pulmonary  artery 

/ 

Right  auricular  appendage -j-^-'~ 


Right  ventricle V  -  T-.  -  •*•  - 


Left  carotid  artery 
Left  subclavian  artery 

Ductus  arteriosus 


i   \  Branches  of  left 
*      '7  pulmonary  artery 


SsMll""'  -----  Left  auricular  appendage 


Left  ventricle 


Descending  aorta 


FIG.  207. — Ventral  view  of  heart  of  foetus  at  term.     Kollmann's  Atlas. 

• 

to  function  and  the  placental  blood  is  cut  off,  so  that  the  right  atrium  receives 
venous  blood  only  and  the  left  arterial  blood  only.  If  the  foramen  ovale  were  to 
persist  it  would  allow  a  mingling  of  venous  and  arterial  blood.  Consequently 
the  foramen  ovale  closes  soon  after  birth  and  the  two  currents  of  blood  are  com- 
pletely separated.  At  the  same  time  the  ductus  arteriosus  atrophies  and  be- 
comes the  ligamentum  arteriosum.  Consequently  there  is  no  direct  communica- 
tion between  the  pulmonary  artery  and  aorta. 

Certain  features  of  development  have  an  important  bearing  on  the  theories  regarding  the 
physiology  of  the  heart,  particularly  on  the  theory  that  the  heart  is  an  automatic  organ. 
Whether  the  theory  that  the  heart  beats  automatically,  i.e.,  independently  of  stimuli  from 
the  nervous  system,  is  true  or  not,  it  is  a  fact  that  in  the  embryo  it  begins  to  beat  before  any 


THE   DEVELOPMENT  OF  THE  VASCULAR  SYSTEM. 


235 


nerve  cells  appear  in  it  and  before  any  nerve  fibers  are  connected  with  it.  At  least  no  technic 
has  yet  been  devised  by  which  it  is  possible  to  demonstrate  nerve  cells  in,  or  fibers  connected 
with  it,  at  the  time  when  it  begins  to  perform  its  characteristic  function.  And,  furthermore, 
at  the  time  when  the  heart  begins  to  beat,  no  heart  muscle  cells  are  developed.  This  last 
fact  seems  to  indicate  an  inherent  contractility  in  the  mesothelial  cells  which  form  the  anlage 
of  the  myocardium. 


Sup.  vena  cava 


Right  atrium-  — fi~- 


Right  ventricle 


Inf.  vena  cava 


Inf.  vena  cava 


>  Pulmonary  veins 


Left  atrium 


—  Left  ventricle 


FIG.  208. — Dorsal  half  of  foetal  heart.     Bumm,  Kollmann's  Atlas. 


The  Vessels. 

Origin. — It  has  already  been  stated  at  the  beginning  of  this  chapter  that  the 
heart  and  blood  vessels  arise  independently,  and  only  secondarily  come  into 
close  relationship.  The  heart  has  its  origin  inside  the  embryo;  the  first  vessels 
and  first  blood  cells,  on  the  other  hand,  have  their  origin  in  the  extraembryonic 
area  of  the  germ  layers.  In  the  chick  embryo  toward  the  end  of  the  first  day  of 
incubation,  the  peripheral  part  of  the  area  opaca  presents  a  reticulated  appear- 
ance when  seen  from  the  surface  (Fig.  209).  Sections  of  the  blastoderm  show 
that  this  appearance  is  due  to  thickenings  in  the  mesoderm,  and  that  at  this 
stage  there  is  no  ccelom  in  this  region  (Fig.  210).  The  thickenings,  however, 
are  situated  rather  nearer  the  entodermal  side,  and  after  the  mesoderm  splits 


230 


TEXT-BOOK  OF  EMBRYOLOGY. 


FIG.  209. — Surface  views  of  chick  blastoderms.     Ruckert,  Hertwig 

a,  Blastoderm  with  primitive  streak  and  head  process;  showing  blood  islands  (dark  spots  increscent- 

shaped  area  in  lower  part  of  figure). 

b,  Blastoderm  with  6  pairs  of  primitive  segments.     Reticulated  appearance  is  due  to  blood  islands 

(dark  spots)  and  to  developing  vessels  the  entire  reticulated  area  being  the  area  vasculosa. 


Blood  island 


FIG.  210. — Section  of  blastoderm  (area  opaca)  of  chick  of  27  hours'  incubation.     Photograph. 


THE   DEVELOPMENT   OF  THE   VASCULAR   SYSTEM. 


237 


into  visceral  and  parietal  layers,  come  to  lie  in  the  visceral  (splanchnic)  layer 
(Fig.  211).  They  are  composed  of  masses  of  cells  known  as  blood  islands  which 
are  the  anlagen  of  both  the  blood  cells  and  the  endothelium  of  the  blood  vessels. 
The  superficial  cells  of  an  island  become  transformed  into  flat  cells  which  sur- 
round the  remaining  cells  of  the  island  and  form  the  endothelial  walls  of  a 
primitive  blood  vessel  (Fig.  211).  A  number  of  these  vessels  then  anastomose  to 
forma  net- work  of  channels  containing,  at  intervals,  groups  of  cells  which  repre- 
sent the  central  cells  of  the  blood  islands,  and  which  are  the  forerunners  of  the 


Ccelom 


Parietal  mesoderm 


Ectoderm 


DC  E   •- ,, 


•    ' 


-    -     - 


Visceral  mesoderm 


Blood  islands 


FIG.  211. — Section  of  blastoderm  of  chick  of  42  hours'  incubation.  Photograph.  The  cells  of  the 
blood  islands  are  differentiated  into  nucleated  red  blood  cells  (erythroblasts)  and  the  endo- 
thelium of  the  vessels. 


red  blood  cells.  Around  the  border  of  the  area  vasculosa  the  vascular  channels 
then  unite  to  form  a  vessel — the  sinus  terminalis — which  is  continuous  except  at 
the  head  end  of  the  embryo  (Fig.  212).  During  the  second  day  of  incubation 
the  vascularization  of  the  splanchnic  layer  of  mesoderm  gradually  extends 
through  the  area  pellucida  toward  the  embryo  (Fig.  212).  Some  of  the  channels 
become  larger  and  form  arteries  and  veins  which  extend  into  the  embryo  and 
finally  unite  with  the  heart  in  a  definite  way  (p.  224). 

The  question  of  the  growth  of  blood  vessels  is  not  yet  settled.  Are  they  formed  by  a 
progressive  differentiation  of  the  mesenchymal  tissue,  or  do  they  grow  out  as  sprouts  or  buds 
from  vessels  already  present  ?  It  is  obvious  that  the  first  vessels  in  the  area  opaca  are 
formed  in  situ  by  a  differentiation  of  the  tissue  already  present.  In  the  vascularization 
of  the  area  pellucida,  do  the  new  vessels  represent  independently  formed  structures  which 
unite  secondarily  with  those  of  the  area  opaca,  or  are  they  the  result  of  outgrowths  from 
the  primary  vessels  in  the  area  opaca  ?  This  same  question  arises  in  regard  to  the  for- 
mation of  the  first  vessels  inside  the  embryonic  body,  and  in  fact  in  regard  to  the  formation 


238 


TEXT-BOOK  OF  EMBRYOLOGY. 


of  new  vessels  so  long  as  any  tissue  of  the  body  continues  to  grow  and  become  vascular.  In 
the  formation  of  the  larger  vascular  trunks  in  the  body  there  is  evidence  to  support  the 
view  that  the  vessels  arise  independently,  for  in  some  cases  at  least  cavities,  lined  by  flat 
cells  appear  in  the  mesenchyme,  which  are  at  first  quite  unconnected,  and  only  secondarily 
unite  to  form  a  continuous  vessel.  On  the  other  hand,  in  the  case  of  the  formation  of  granu- 
lation tissue  or  any  new  tissue,  including  pathological  growths,  it  is  usually  held  that  the 


FlG.  212. — Surface  view  of  chick  embryo  with  18  pairs  of  primitive  segments,  including  the 

area  vasculosa.     Riickert,  Hertwig. 

The  reticulum  indicates  the  blood  vessels;  the  dark  spots  in  the  vessels  being  blood  islands      The 
darker  line  at  the  border  of  the  figure  represents  the  sinus  terminalis. 


new  vessels  arise  as  outgrowths  from  other  vessels:  The  endothelium  of  a  vessel  proliferates 
and  grows  out  as  a  slender  process  which  becomes  hollow  and  thus  forms  a  capillary  con- 
tinuous with  the  original  vessel  from  which  it  is  an  outgrowth. 

Some  of  the  larger  channels  of  the  area  vasculosa  converge  to  form  a  single 
vessel  on  each  side,  which  enters  the  embryonic  body  through  the  splanchno- 
pleure  and  joins  the  caudal  end  of  the  heart  (p.  224).  These  two  vessels  are 
known  as  the  omphalomesenteric  (vitelline)  veins  (Fig.  213).  Other  channels  of 


THE   DEVELOPMENT   OF  THE   VASCULAR  SYSTEM. 


239 


the  area  vasculosa  converge  to  form  another  pair  of  vessels,  the  omphalomesen- 
teric  (vitelline)  arteries,  which  extend  into  the  embryo  through  the  splanchno- 
pleure  until  they  reach  a  point  ventro-lateral  to  the  notochord,  thence  extend 
cranially  and  caudally  as  the  two  primitive  aorta.  Later  as  the  germ  layers 
close  in  ventrally,  these  fuse  longitudinally,  except  in  the  cervical  region,  to 
form  the  single  dorsal  aorta.  The  proximal  ends  of  the  omphalomesenteric 
arteries  also  fuse  into  a  single  trunk  which  may  then  be  considered  as  a  branch 
of  the  aorta.  The  double  portion  of  the  aorta  in  the  cervical  region  sends  a 


Aortic  arches 


Heart 


Sinus  terminalis 


Sinus 
terminalis  *~i 


Sinus 
venosus 


Right  vitelline  vein 
Right  vitelline  artery 


Ant.  cardinal 
vein 


Aorta 


Duct  of  Cuvier 
Post,  cardinal  vein 
Left  vitelline  artery 


Left  vitelline  vein 


FIG.  213. — Diagram  of  the  vitelline  (yolk)  circulation  of  a  chick  embryo  at  the  end 
of  the  third  day  of  incubation.     Balfour. 


branch  ventrally  on  each  side  through  each  branchial  arch,  forming  the  aortic 
arches.  The  aortic  arches  on  each  side  then  unite  ventrally  to  form  the  ventral 
aortic  root,  and  the  two  ventral  aortic  roots  unite  in  the  medial  line  to  form  the 
single  ventral  aortic  trunk  which  joins  the  cranial  end  of  the  heart  (p.  224). 
Thus  the  vitelline  (or  yolk)  circulation  is  completed.  And  from  this  time  on,  the 
area  vasculosa  gradually  enlarges,  as  the  mesoderm  extends  farther  and  farther 
around  the  yolk,  until  finally  it  surrounds  the  entire  mass  of  yolk. 

In  Mammals,  as  in  the  chick,  the  vascular  anlagen  first  appear  in  the  extra- 

16 


240 


TEXT-BOOK  OF  EMBRYOLOGY. 


Flo.  214. — Surface  view  of  area  vasculosa  of  a  rabbit  embryo  of  n  days,  van  Beneden  and  Julin. 
The  vessel  around  the  border  is  the  sinus  terminalis;  the  two  large  vessels  above  the  embryo  are 
the  vitelline  (omphalomesenteric)  veins;  the  two  large  vessels  converging  below  the  embryo 
are  the  vitelline  (omphalomesenteric)  arteries. 


Dors,  aortic  root 
and  aortic  arches 


Ant.  cardinal  vein 


Chorionic  villi 


FIG.  215. — Human  embryo  of  3.2  mm.     His.     The  arrows  indicate  the 
direction  of  the  blood  current. 


THE   DEVELOPMENT  OF  THE  VASCULAR   SYSTEM. 


241 


embryonic  area.  In  the  rabbit  they  begin  to  develop  about  the  eighth  day.  A 
reticulated  area  appears  in  the  peripheral  part  of  the  area  opaca  and  in  a  short 
time  shows  an  anastomosing  network  of  channels,  in  which  lie  the  blood 
islands.  The  network  then  gradually  extends  toward  the  embryo  and  some  of 
the  channels  converge  to  form  a  pair  of  omphalomesenteric  veins  and  a  pair  of 
omphalomesenteric  arteries,  which  behave  in  the  same  manner  as  in  the  chick 


Int.  carotid  artery 


Vertebral  artery 


Vitelline  vein 
Vitelline  artery 

Umbilical  vein 

Umbilical 

arteries 


Duct  of  Cuvier 


Post,  cardinal 
vein 


Aorta 


Post,  cardinal  vein 


FIG,  216. — Reconstruction  of  a  human  embryo  of  7  mm.     Matt. 

Arteries  represented  in  black.  A.  V.,  Auditory  vesicle;  ZJ>  bronchus;  L,  liver;  K,  anlage  of 
kidney;  T,  thyreoid  gland;  III— XII.  cranial  nerve  roots;  i,  2,  3,  4,  branchial  grooves; 
i,  8,  12,  5  (on  spinal  nerve  roots),  ist  and  8th  cervical,  i2th  dorsal,  5th  lumbar  spinal 
nerves  respectively.  Dotted  outlines  represent  limb  buds. 

(Fig.  214).     The  area  vasculosa  then  gradually  enlarges  until  it  embraces  the 
entire  yolk  sac. 

There  are  no  observations  on  the  early  formation  of  the  vascular  anlagen  in 
the  human  embryo,  but  it  is  reasonable  to  suppose  they  appear  in  the  same 
manner  as  in  other  Mammals.  In  an  embryo  in  which  there  is  no  trace  even  of 
a  neural  plate  (Peters'  embryo,  see  p.  90  and  Fig.  82),  the  vascular  area 


242 


TEXT-BOOK  OF  EMBRYOLOGY. 


embraces  the  entire  yolk  sac,  and  this  fact  indicates  a  precocious  development  of 
the  vascular  anlagen.  In  an  embryo  of  3.2  mm.  the  vitelline  circulation  is 
complete.  A  study  of  Fig.  215  will  assist  in  understanding  the  similarities 
between  the  early  form  of  circulation  in  the  human  embryo  and  the  other  forms 
which  have  been  considered.  It  is  thus  seen  that  the  earliest  form  of  circulation 
in  man,  as  well  as  in  lower  forms,  is  associated  with  the  yolk  sac. 

In  animals  below  the  Mammals,  where  a  large  amount  of  yolk  is  present, 
the  vitelline  circulation  is  of  great  importance  in  supplying  the  growing  embryo 
with  nutritive  materials.  In  Mammals,  where  there  is  little  yolk  present,  the 


Gut 


Umbilical  vein 


Amnion 


Allantois 


Yolk  stalk 


Umbilical  artery 
Umbilical  vein 

Amnion 


Chorionic  villi 


FIG.  217. — Diagram  of  the  umbilical  vessels  in  the  belly  stalk  and  chorion.    Kollmann's  Atlas. 


vitelline  circulation  is  of  short  duration  and  minor  importance,  yet  those  por- 
tions of  the  vessels  inside  the  embryo  play  a  part  in  the  further  development  of 
the  vascular  system.  Again,  in  Reptiles  and  Birds,  a  second  circulation,  as  it 
were,  develops  in  connection  with  the  allantois,  and  persists  during  incubation, 
since  the  allantois  is  a  reservoir  for  the  waste  products  of  the  body.  In  Mam- 
mals, however,  the  allantois  is  rudimentary,  its  place  being  taken  by  the  pla- 
centa which  establishes  the  communication  between  the  embryo  and  the  mother; 
and  the  vessels  which  correspond  to  the  allantoic  vessels  in  Reptiles  and  Birds 
become  associated  with  the  placental  circulation.  Two  arteries,  one  on  each 


THE  DEVELOPMENT   OF  THE  VASCULAR  SYSTEM. 


243 


side,  arise  from  the  dorsal  aorta  in  the  lumbar  region  of  the  embryo  and  pass  out 
through  the  belly  stalk  (later  the  umbilical  cord)  to  end  in  the  chorionic  villi. 
These  are  known  as  the  allantoic  or  umbilical  arteries.  The  blood  from  the 
chorionic  villi  is  carried  back  to  the  embryo  by  the  umbilical  veins  which, 
although  a  single  trunk  in  the  umbilical  cord,  pass  cranially  through  the  body  wall, 
one  on  each  side,  and  open  into  the  ducts  of  Cuvier  (Figs  216  and  217).  The 
course  and  distribution  of  the  blood  vessels  in  the  placenta  have  been  considered 
in  the  chapter  on  foetal  membranes  (see  p.  131). 

The  Arteries. — The  simplest  form  of  the  arterial  system  is  as  follows: 
The  single  dorsal  aorta  extends  from  the  cervical  region  to  the  caudal  end  of 
the  embryo  and  is  situated  in  the  medial  line  ventral  to  the  notochord.  In  the 
cervical  region  a  branch  extends  cranially  on  each  side  of  the  medial  line,  the 
two  forming  the  dorsal  aortic  roots.  From  the  latter,  other  branches  arise  and 


Dors,  aortic  root 


Dors,  aortic  root 


Vent,  aortic  root 

Vent,  aortic  trunk    "  V  \       "i-> 

'• -    Pulmonary  artery 

FIG.  218. — From  reconstruction  of  aortic  arches  (i,  2,  3,  4,  6,)  of  left  side  and 

pharynx  of  a  5  mm.  human  embryo.     Tandler. 

I-IV;  Inner  branchial  grooves. 

pass  ventrally,  one  in  each  branchial  arch,  forming  the  aortic  arches.  These 
unite  ventrally  on  each  side  to  form  a  single  vessel,  the  ventral  aortic  root, 
and  the  two  roots  unite  to  form  the  single  ventral  aortic  trunk  which  joins  the 
cranial  end  of  the  heart.  Somewhat  caudal  to  the  middle  of  the  embryo  a 
branch  of  the  aorta  passes  ventrally  through  the  mesentery  as  the  omphalomes- 
enteric  artery  which  enters  the  umbilical  cord.  Still  farther  caudally  the 
paired  umbilical  (allantoic)  arteries  are  given  off  from  the  aorta  and  pass  out 
into  the  umbilical  cord  (Figs.  215,  216,  217). 

The  conditions  which  exist  at  this  stage  in  the  region  of  the  aortic  arches  in 
mammalian  embryos  are  indicative  of  the  conditions  which  persist  as  a  whole 
or  in  part  throughout  life  in  the  lowest  Vertebrates.  The  changes  which  occur 
in  Mammals,  however,  are  profound  and  the  adult  condition  bears  no  resem- 
blance to  the  embryonic.  Yet  certain  features  in  the  adult  are  intelligible  only 
from  a  knowledge  of  their  development.  In  the  human  embryo  six  aortic  arches 


244 


TEXT-BOOK  OF  EMBRYOLOGY. 


appear  on  each  side.  The  first,  second,  third,  and  fourth  pass  through  the 
corresponding  branchial  arches.  The  fifth  arch,  which  is  merely  a  loop  from 
the  fourth,  seems  to  pass  through  the  fourth  branchial  arch.  The  sixth  aortic 
arch  passes  through  the  region  behind  the  fourth  branchial.  All  these  arches  are 
present  in  embryos  of  5  mm.  (Fig.  218).  In  Fishes  and  larval  Amphibians,  where 
the  branchial  arches  develop  into  the  gills,  the  aortic  arches  are  broken  up  into 
capillary  networks  which  ramify  in  the  gills,  and  the  ventral  aortic  root  becomes 
the  afferent  vessel,  the  dorsal  aortic  roots  the  efferent  vessels.  In  the  higher 
Vertebrates  and  in  man  the  aortic  arches  begin,  at  a  very  early  period,  to 
undergo  changes;  some  disappear  and  others  become  portions  of  the  large 

Vent,  aortic  roots 


VI 
Dorsal  aortic  roots 


Aorta 


Subclavian  arteries 


FIG.  219.— Diagram  of  the  aortic  arches  of  a  Mammal.     Modified  from  Hochstetter. 

arterial  trunks  which  leave  the  heart.  In  connection  with  the  following 
description,  constant  reference  to  Figs.  219  and  220  will  assist  the  student  in 
understanding  the  changes. 

The  first  and  second  arches  soon  atrophy  and  disappear.  The  third 
arch  on  each  side  becomes  the  proximal  part  of  the  internal  carotid  artery,  while 
the  continuation  of  the  dorsal  aortic  root,  cranially  to  the  third  arch,  becomes 
its  more  distal  part.  The  continuation  of  the  ventral  aortic  root  cranially  to  the 
third  arch,  becomes  the  proximal  part  of  the  external  carotid  artery,  while  the 
portion  of  the  ventral  aortic  root  between  the  third  and  fourth  arches  becomes 
the  common  carotid  artery.  The  portion  of  the  dorsal  aortic  root  between  the 


THE   DEVELOPMENT  OF  THE   VASCULAR  SYSTEM 


245 


third  and  fourth  arches  disappears.  The  fourth  aortic  arch  on  the  left  side 
enlarges  and  becomes  the  arch  of  the  aorta  (arcus  aorlce)  which  is  then  continued 
caudally  through  the  left  dorsal  aortic  root  into  the  dorsal  aorta.  On  the  right 
side,  the  fourth  arch  becomes  the  proximal  part  of  the  subdavian  artery.  Since 
the  third,  fourth,  fifth,  and  sixth  arches  really  leave  the  ventral  aortic  trunk  as  a 
single  vessel,  it  will  be  seen  that  these  changes  bring  it  about  that  the  common 
carotid  and  subclavian  on  the  right  side  arise  by  a  common  stem,  the  innomi- 
nate artery,  which  in  turn  is  a  branch  of  the  arch  of  the  aorta.  On  the  left  side, 


Common  carotid  arteries 


Int.  carotid  artery  (right)  - 
Ext.  carotid  artery  (right) 

I 

II  '. 
Int.  carotid  III 

Subclavian  IV 

V 

VI 

Innominate  artery 

Subclavian  artery  (right) 


Int.  carotid  artery  (left) 
Ext.  carotid  artery  (left) 


II 

III  Int.  carotid 

IV  Arch  of  aorta 
V 

VI  Ductus  arteriosus 


Pulmonary  artery 
Subclavian  artery  (left) 
Aorta 


FIG.  220. — Diagram  representing  the  changes  in  the  aortic  arches  of  a  Mammal. 
Compare  with  Fig.  219.     Modified  from  Hochstetter. 


for  the  same  reason,  the  common  carotid  is  a  branch  of  the  arch  of  the  aorta. 
The  fifth  aortic  arch  from  the  beginning  is  rudimentary  and  disappears  very 
early.  The  sixth  arch  on  each  side  undergoes  wide  changes.  A  branch  from 
each  enters  the  corresponding  lung.  On  the  right  side  the  portion  of  the  sixth 
arch  between  the  branch  which  enters  the  lung  and  the  dorsal  aortic  root  disap- 
pears, as  does  also  that  portion  of  the  right  dorsal  aortic  root  between  the 
subclavian  artery  and  the  original  bifurcation  of  the  dorsal  aorta.  On  the 
left  side,  however,  that  portion  of  the  sixth  arch  between  the  branch  which 
enters  the  lung  and  the  dorsal  aortic  root  persists  until  birth  as  the  ductus 


246 


TEXT-BOOK  OF  EMBRYOLOGY. 


arteriosus  (Botalli).  This  conveys  the  blood  from  the  right  ventricle  to  the 
aorta  until  the  lungs  become  functional  (Fig.  207);  it  then  atrophies  and  be- 
comes the  ligamenlum  arteriosum.  In  the  meantime  the  septum  aorticum  has 
divided  the  original  ventral  aortic  trunk  into  two  vessels  (see  p.  230) ;  one  of  the 
vessels  communicates  with  the  left  ventricle  and  is  the  proximal  part  of  the 
arch  of  the  aorta,  the  other  communicates  with  the  right  ventricle  and  be- 
comes the  large  pulmonary  artery  (Fig.  203) . 

In  human  embryos  of  10  mm.  the  dorsal  aortic  root  on  each  side  gives  off 
several  lateral  branches — the  segmental  cervical  vessels  (Fig.  221).  The  first 
of  these  (first  cervical,  suboccipital),  which  arises  nearly  opposite  the  fourth 
aortic  arch,  is  a  companion,  as  it  were,  to  the  hypoglossal  nerve,  and  sends  a 
branch  cranially  which  unites  with  its  fellow  of  the  opposite  side  inside  the  skull 
to  form  the  basilar  artery.  The  basilar  artery  again  bifurcates  and  each  branch 


Int.  carotid  artery 


Vertebral  artery 


....  Segmental  cervical  artery 


Pulmonary  artery 

FIG.  221. — Diagram  of  the  aortic  arches  (III,  IV,  VI)  and  segmental  cervical  arteries 
of  a  10  mm.  human  embryo.    His. 

unites  with  the  corresponding  internal  carotid  by  means  of  the  circulus  arteriosus 
(Fig.  223).  The  other  segmental  cervical  vessels  arise  from  the  aortic  root 
at  intervals,  the  eighth  arising  near  the  point  of  bifurcation  of  the  aorta.  In  a 
short  time  a  longitudinal  anastomosis  appears  between  these  segmental  arteries, 
which  extends  as  far  as  the  seventh  (Fig.  222).  The  proximal  ends  of  the  first 
six  disappear,  and  the  longitudinal  vessel  forms  the  vertebral  artery  which  then 
opens  into  the  aortic  root  through  the  seventh  segmental  artery,  and  which  is 
continued  cranially  as  the  basilar  artery  (Fig.  223).  The  seventh  (it  is  held  by 
some  to  be  the  sixth)  segmental  artery  becomes  the  subclavian,  and  conse- 
quently the  vertebral  opens  into  the  subclavian,  as  in  the  adult  (Fig.  222).  But 
it  should  be  borne  in  mind  that  the  right  subclavian  artery  is  more  than  equiva- 
lent to  the  left,  since  the  proximal  part  of  the  former  is  made  up  of  the  fourth 
aortic  arch  and  a  part  of  the  aortic  root  (see  Figs.  219  and  220).  Further- 
more, changes  occur  in  the  position  of  the  heart  during  development,  which 


THE  DEVELOPMENT  OF  THE   VASCULAR  SYSTEM. 


247 


alter  the  relations  of  the  vessels.  The  heart  migrates  from  its  original  position 
in  the  cervical  region  into  the  thorax,  and  this  produces  an  elongation  of  the 
carotid  arteries  and  an  apparent  shortening  of  the  arch  of  the  aorta;  conse- 


.  carotid 


id—  — 


Vert. 


;^» 

x-'-'-^C 


-5ub.  inter, 
art. 


FIG.  222. — Diagram  illustrating  the  formation  of  the  vertebral  and  superior  intercostal  arteries. 
The  broken  lines  represent  the  portions  of  the  original  segmental  vessels  that  disappear. 
Modified  from  Hochstetter. 

quently  the  subclavian  artery  on  the  left  side  arises  relatively  nearer  the  heart. 

The  arteries  of  the  brain  arise  as  branches  of  the  internal  carotid  and  circu- 

lus  arteriosus.     The  anterior  cerebral  artery  and  the  middle  cerebral  artery  arise 


Circulus  arteriosus 


Middle  cerebral 
artery 


Basilar  artery 
Int.  carotid  artery 


FIG.  223. — Brain  and  arteries  of  a  human  embryo  of  9  mm.     Matt. 

primarily  from  a  common  stem  which  in  turn  is  a  branch  of  the  most  cranial 
part  of  the  internal  carotid  (Figs.  223  and  224).  The  posterior  cerebral  artery 
arises  as  a  branch  of  the  circulus  arteriosus  (Fig.  224). 


248 


TEXT-BOOK  OF  EMBRYOLOGY. 


From  the  point  of  its  bifurcation  to  its  caudal  end  the  aorta  gives  off  paired, 
segmental  branches  which  accompany  the  segmental  nerves.  The  last  (eighth) 
cervical  branch  and  the  first  two  thoracic  branches  undergo  longitudinal  anas- 
tomoses, similar  to  those  between  the  first  seven  cervical,  to  form  the  superior 
intercostal  artery  (A.  intercostalis  suprema)  which  opens  into  the  subclavian 
(Fig.  222).  The  other  thoracic  branches  persist  as  the  intercostal  arteries;  the 
lumbar  branches  persist  as  the  lumbar  arteries.  At  the  same  time  anastomoses 
are  formed  between  the  distal  ends  of  the  intercostal  and  lumbar  arteries  in 
the  ventro-lateral  region  of  the  body  wall,  which  give  rise,  on  the  one  hand,  to  the . 
internal  mammary  artery  and,  on  the  other  hand,  to  the  inferior  epigastric  artery. 
Of  these  two  the  former  opens  into  the  subclavian,  the  latter  into  the  external 
iliac.  By  a  further  anastomosis  the  distal  ends  of  the  internal  mammary  and 
inferior  epigastric  are  joined,  thus  forming  a  continuous  vessel  from  the  sub- 


Post,  cerebral  vein 
(sup.  petrosal  sinus) 


Circulus  arteriosus 
Transverse  sinus 

Basilar  artery 
Int.  jugular  vein 


Confluence  of  sinuses 

Inf.  sagittal  sinus 
Sup.  sagittal  sinus 
Post,  cerebral  artery 

Ant.  cerebral  artery 
Int.  carotid  artery 


FIG.  224. — Brain,  arteries  and  veins  of  a  human  embryo  of  33  mm.     Mall. 


clavian  to  the  external  iliac  (Fig.  225).  It  is  interesting  to  note  that  while 
originally  all  the  lateral  branches  of  the  aorta  are  arranged  segmentally,  many 
of  them  lose  their  segmental  character  and  are  replaced  or  supplemented  by 
longitudinal  vessels. 

In  addition  to  the  lateral  segmental  branches  of  the  aorta,  which  have  been 
described,  other  branches  develop  which  carry  blood  to  the  viscera.  A  num- 
ber of  these,  or  possibly  all,  are  also  primarily  segmental  vessels,  although  they 
lose  every  trace  of  their  segmental  character  during  development.  The  first  of 
the  visceral  branches  to  appear  is  the  omphalomesenteric  artery  which  arises 
from  the  ventral  side  of  the  aorta  and  which  has  been  mentioned  in  connection 
with  the  vitelline  circulation.  Originally  it  passes  out  through  the  mesentery 
and  follows  the  yolk  stalk  to  ramify  on  the  surface  of  the  yolk  sac.  But  since 
the  yolk  sac  is  of  slight  importance,  the  distal  part  of  the  artery  soon  disappears, 
while  the  proximal  part  becomes  the  superior  mesenteric  artery  (Fig.  226).  The 


THE   DEVELOPMENT   OF  THE   VASCULAR   SYSTEM. 


249 


cceliac  artery  arises  from  the  ventral  side  of  the  aorta  a  short  distance  cranially 
to  the  omphalomesenteric  (Fig.  226)  and  gives  rise  in  turn  to  the  gastric,  hepatic 
and  splenic  arteries.  The  inferior  mesenteric  artery  also  arises  from  the  ventral 
side  of  the  aorta  some  distance  caudal  to  the  omphalomesenteric  (Fig.  226). 
In  the  early  stages  these  visceral  arteries  arise  relatively  much  farther  cranially 
than  in  the  adult.  During  development  they  gradually  migrate  caudally  to 
their  normal  positions. 


Int.  mammary  artery 


Inf.  epigastric  artery 


Umbilical  artery 


Femoral  artery 


FIG.  225. — Diagram  of  human  embryo  of  13  mm.,  showing  the  mode  of  development 
of  the  internal  mammary  and  inferior  epigastric  arteries.     Mall. 

Other  branches  of  the  aorta  develop  in  connection  with  the  urinary  and 
genital  organs,  and,  with  the  possible  exception  of  the  renal  arteries,  they  are 
primarily  segmental  in  character.  Several  branches  supply  the  mesonephroi, 
but  when  the  latter  atrophy  and  disappear  the  vessels  also  disappear.  The 
renal  arteries  do  not  develop  until  the  kidneys  have  practically  reached  their 
final  position  in  the  embryo,  and  then  they  arise  directly  from  the  aorta.  Dur- 
ing the  development  of  the  genital  glands  several  pairs  of  branches  from  the 
aorta  supply  them  with  blood.  Later  the  majority  of  these  vessels  disappear, 
one  pair  only  persisting  as  the  internal  spermatic  arteries  which  differ  in  accord- 
ance with  the  sex  of  the  individual.  In  both  sexes  they  are  at  first  very  short; 


250 


TEXT-BOOK  OF  EMBRYOLOGY. 


in  the  female,  as  the  ovaries  move  farther  into  the  pelvic  region,  they  become 
considerably  elongated  to  form  the  ovarian  arteries;  in  the  male,  with  the 
descent  of  the  testes,  they  become  very  much  elongated  to  form  the  testicular 
arteries. 

The  fourth  (or  fifth?)  pair  of  segmental  lumbar  arteries  primarily  gives 
rise  to  the  vessels  which  supply  the  lower  extremities,  viz.,  the  iliac  arteries. 
These  then  would  be  serially  homologous  to  the  subclavians.  But  certain 
changes  occur  in  this  region,  which  are  due  to  the  relations  of  the  um- 
bilical arteries.  The  latter,  as  has  already  been  noted,  arise  as  paired 
branches  of  the  aorta  in  the  lumbar  region,  pass  ventrally  through  the  genital 
cord  (Chap.  XV)  and  then  follow  the  allantois  (urachus)  to  the  umbilical  cord. 


Coeliac  artery 


Sup.  mesenteric 
(vitelline)  artery 


Umbilical  artery 


Aorta 


Duodenum 

Inf.  mesenteric  artery 
Int.  iliac  artery 


FIG.  226. — Diagram  of  the  visceral  arteries  in  a  human  embryo  of  12.5  mm.     Tandler. 
Numerals  indicate  segmental  arteries. 


During  fcetal  life  they  carry  all  the  blood  that  passes  to  the  placenta.  At  an 
early  period  a  branch  from  each  iliac  artery  anastomoses  with  the  corresponding 
umbilical,  and  the  portion  of  the  umbilical  artery  between  the  aorta  and  the 
anastomosis  then  disappears.  This  makes  the  umbilical  artery  a  branch  of 
the  iliac;  and  the  blood  then  passes  from  the  aorta  into  the  proximal  part  of 
the  iliac  which  becomes  the  common  iliac  artery  of  the  adult.  At  birth,  when  the 
umbilical  cord  is  cut,  the  umbilical  arteries  no  longer  carry  blood  to  the  placenta, 
and  their  intraembryonic  portions,  often  called  the  hypogastric  arteries,  persist 
only  in  part;  their  proximal  ends  persist  as  the  superior  vesical  arteries,  while 
the  portions  which  accompanied  the  urachus  degenerate  to  form  the  lateral 
umbilical  ligaments. 


THE   DEVELOPMENT  OF  THE   VASCULAR  SYSTEM. 


251 


So  far  as  a  complete  history  of  the  growth  of  the  arteries  of  the  extremities  is 
concerned,  knowledge  is  lacking.  The  facts  of  comparative  anatomy  and  the 
anomalies  which  occur  in  the  human  body  have  led  to  certain  conclusions  which 
have  been  largely  confirmed  by  embryological  observations;  but  much  more 
work  on  the  development  of  the  arteries  is  yet  necessary  to  complete  their 
history.  The  extremities  represent  outgrowths  from  several  segments  of  the 
body,  and  the  nerve  supply  is  derived  from  several  segments,  but  the  blood  is 
furnished  by  a  single  segmental  vessel  in  each  extremity.  In  the  upper  ex- 
tremity the  subclavian,  which  represents  the  seventh  cervical  branch  of  the 
aortic  root,  is  the  primary  vessel  from  which  all  the  other  vessels  are  derived.  In 


Brachial  artery- 


Superficial  radia  artery 


Median  artery 

Interosseous  artery 

Ulnar  artery  -• 


Brachial  artery 


B 


-----  Median  artery 

Interosseous  artery 

•-•  Ulnar  artery 
*  *  Radial  artery 


FIG.  227. — Diagrams  showing  (^4)  an  early  and  (B)  a  late  stage  in  the  development 
of  the  arteries  of  the  upper  extremity.     McMurrich. 

the  lower  extremity  the  common  iliac,  which  represents  the  fourth  (or  fifth?) 
lumbar  branch  of  the  aorta  is  the  primary  vessel. 

In  the  upper  extremity  the  subclavian  grows  as  a  single  vessel  to  the  wrist 
and  then  divides  into  branches  corresponding  to  the  fingers.  In  the  forearm  it 
lies  between  the  radius  and  ulna.  In  a  short  time  a  branch  is  given  off  just 
distal  to  the  elbow  and  accompanies  the  median  nerve.  As  this  branch  in- 
creases, the  original  vessel  in  the  forearm  diminishes  to  form  the  volar  inter- 
osseous  artery;  and  at  the  same  time  the  branch  unites  again  with  the  lower  end  of 
the  interosseous,  takes  up  the  digital  branches  and  becomes  the  chief  vessel  of 
the  forearm  at  this  stage,  forming  the  median  artery.  Later,  however,  it  di- 
minishes in  size  as  another  vessel  develops,  the  ulnar  artery,  which  arises  a  short 


252 


TEXT-BOOK  OF  EMBRYOLOGY. 


distance  proximal  to  the  origin  of  the  median  and,  passing  along  the  ulnar  side 
of  the  forearm,  unites  with  the  median  to  form  the  superficial  volar  arch.  From 
the  artery  of  the  arm,  which  is  called  the  brachial  artery,  a  branch  develops 
about  the  middle  and  extends  distally  along  the  radial  side  of  the  forearm.  A 
little  later  another  branch  grows  out  from  the  brachial  just  proximally  to  the 
origin  of  the  ulnar  and  extends  across  to,  and  anastomoses  with,  the  first  branch. 
Then  the  portion  of  the  first  branch  between  its  point  of  origin  and  the  anasto- 
mosis atrophies,  leaving  only  a  small  vessel  which  goes  to  the  biceps  muscle. 
The  second  branch  and  the  remaining  part  of  the  first  branch  together  form  the 
radial  artery  (Fig.  227)  (McMurrich). 


Femoral  artery  ,- 


Sciatic  artery  •«.— 


Popliteal  artery  •<.-  — 


Peroneal  artery  ^c 

Saphenous  artery  -- 

Dors,  artery  of  foot  -- 


n 


.sciatic  artery 


'  Femoral  artery 


•  Popliteal  artery 


Ant.  tibial  artery 

—  Peroneal  artery 
Post,  tibial  artery 


FIG.  228. — Diagrams  showing  three  stages  in  the  development  of  the  arteries 
of  the  lower  extremity.     McMurrich. 

In  the  lower  extremity  the  primary  artery  is  a  continuation  of  the  common  iliac 
which,  in  turn,  is  a  branch  of  the  aorta.  This  primary  vessel,  the  sciatic  artery, 
passes  distally  as  far  as  the  ankle.  Below  the  knee  it  gives  off  a  short  branch 
which  corresponds  to  the  proximal  part  of  the  anterior  tibial  artery.  Just  above 
the  ankle  it  gives  off  another  branch  which  corresponds  to  the  distal  part  of  the 
anterior  tibial.  As  will  be  seen,  these  two  parts  join  at  a  later  period  to  form  a 
continuous  vessel.  At  this  early  stage  the  external  iliac  artery  is  but  a  small 
branch  of  the  common  iliac;  but  it  gradually  increases  in  size,  extends  farther 
distally  in  the  thigh  as  the  femoral  artery  and  unites  with  the  sciatic  near  the 
knee.  Just  proximal  to  its  union  with  the  sciatic  it  gives  off  a  branch  which 
extends  distally  along  the  inner  side  of  the  leg  to  the  plantar  surface  of  the  foot, 
where  it  gives  off  the  digital  branches.  This  vessel  is  the  saphenous  artery  in 
the  embryo,  and  disappears  in  part  during  further  development.  From  this 


THE   DEVELOPMENT  OF  THE  VASCULAR  SYSTEM.  253 

time  on,  the  femoral  and  its  direct  continuation,  the  popliteal,  increase  in  size; 
and  at  the  same  time  the  sciatic  loses  its  primary  connection  and  becomes  much 
reduced  to  form  the  inferior  gluteal  artery.  The  direct  continuation  of  the 
sciatic  in  the  leg,  which  is  now  the  direct  continuation  of  the  popliteal,  becomes 
reduced  to  form  the  peroneal  artery.  The  branch  of  the  original  sciatic,  which 
was  given  off  just  below  the  knee,  unites  with  the  branch  which  was  given  off 
just  above  the  ankle  to  form  a  continuous  vessel,  the  anterior  tibial  artery.  A 
new  branch  arises  from  the  proximal  portion  of  the  peroneal,  extends  down  the 
back  of  the  leg,  anoj  unites  with  the  distal  part  of  the  embryonic  saphenous  to 
form  the  posterior  tibial  artery.  The  proximal  part  of  the  saphenous  then 
atrophies,  leaving  but  one  of  the  small  genu  branches  of  the  popliteal  (Fig.  228) 
(McMurrich). 

The  Veins. — The  changes  which  occur  during  the  development  of  the 
venous  system  are  so  complicated,  and  in  some  cases  so  varied,  that  the  scope  of 
this  book  permits  only  a  brief  outline  of  the  growth  of  the  more  important  of  the 
venous  trunks. 

Corresponding  to  the  arterial  system,  the  first  veins  to  appear  are  the 
omphalomesenteric  veins.  These  vessels,  which  carry  blood  from  the  yolk  sac 
to  the  heart,  arise  in  the  area  vasculosa,  enter  the  embryonic  body  at  the  sides  of 
the  yolk  stalk,  pass  cranially  along  the  intestinal  tract,  and  join  the  caudal  end 
of  the  heart  (Figs.  213,  215,  216,  and  231).  Next  in  point  of  time  to  appear 
are  the  umbilical  veins  which  carry  back  to  the  heart  the  blood  which  has  been 
carried  to  the  placenta  by  the  umbilical  arteries.  These  also  are  paired  veins 
within  the  embryo,  although  they  form  a  single  trunk  in  the  umbilical  cord. 
They  extend  cranially  on  each  side  through  the  ventro-lateral  part  of  the  body 
wall  and  join  the  duct  of  Cuvier  (see  below)  in  the  septum  transversum  (Figs. 
217,  216  and  231).  Very  soon  after  the  appearance  of  the  umbilical  veins 
two  other  longitudinal  vessels  develop,  one  on  each  side  of  the  aorta.  In 
the  cervical  region  they  lie  dorsal  to  the  branchial  arches  and  are  called  the 
anterior  cardinal  veins  (Figs.  215  and  231).  The  more  caudal  parts  of  the 
vessels  are  situated  in  the  region  of  the  developing  mesonephros  and  are  called 
the  posterior  cardinal  veins  (Figs.  215  and  231).  At  a  point  about  opposite  the 
heart  the  anterior  and  posteiior  cardinals  on  each  side  unite  to  foim  a  single 
vessel,  the  duct  of  Cuvier,  which  turn?  medially  through  the  septum  transversum 
and  opens  into  the  sinus  venosus  (Figs.  215  and  216).  Thus  three  primary 
sets  of  veins  are  formed  at  a  very  early  stage  of  development:  (i)  The  omphal- 
omesenteric veins;  (2)  the  umbilical  veins;  (3)  the  cardinal  veins. 

The  veins  of  the  head  and  neck  regions  are  derivatives  of  the  anterior  cardinals. 
The  proximal  parts  of  these  vessels  are  present  in  embryos  of  3.2  mm.;  later  they 
extend  cranially  along  the  ventro-lateral  surface  of  the  brain  on  the  medial  side  of 
the  roots  of  the  cranial  nerves.  The  position  relative  to  the  nerves  is  only  tern- 


254 


TEXT-BOOK  OF  EMBRYOLOGY. 


porary,  however,  for  collaterals  arising  from  the  veins  pass  to  the  lateral  side  of 
the  nerves  and  enlarge  to  form  the  main  channels.  The  original  channels  atrophy 
except  in  the  region  of  the  trigeminal  nerves  where  they  still  remain  on  the 
medial  side  of  the  nerves  as  the  forerunners  of  the  cavernous  sinuses.  The  ves- 
sel thus  formed  laterally  to  the  cranial  nerves  (except  the  trigeminal)  on  each 
side  of  the  brain  is  known  as  the  lateral  vein  of  the  head  (vena  lateralis  capitis) 
(Fig.  229).  The  blood  is  collected  from  the  brain  region  by  small  vessels 
which  unite  to  form  three  main  stems;  one  of  these,  the  superior  cerebral  vein, 
opens  into  the  cranial  end  of  the  cavernous  sinus;  another,  the  middle  cerebral 
vein,  opens  into  the  opposite  end  of  the  cavernous  sinus;  and  the  third,  the 
inferior  cerebral  vein,  opens  into  the  lateral  vein  of  the  head  behind  the  ear 
vesicle  (Figs.  229  and  224).  The  branches  of  the  superior  cerebral  vein  extend 

N.V  N.VII  N.IX 


Mid.  cerebral  vein 


Sup.  cerebral  vein 


Inf.  cerebral  vein 


Lat.  vein  of  head 


Hypoglossal 
(XII)  nerve 


FIG.  229. — Veins  of  the  head  of  a  9  mm.  human  embryo.     Mall. 


over  the  cerebral  hemispheres  and  unite  with  their  fellows  of  the  opposite  side  to 
form  the  superior  sagittal  sinus  which  lies  in  the  medial  line  (Figs.  224  and  230). 
The  superior  sagittal  sinus  is  at  first  naturally  drained  by  the  superior  cerebral 
veins;  but  later,  as  the  cerebral  hemispheres  enlarge  and  extend  farther  toward 
the  mid-brain  region,  it  is  carried  back  and  joins  the  middle  cerebral  vein;  still 
later,  for  the  same  reason,  it  joins  the  inferior  cerebral  vein  (Fig.  230,  A  and  B). 
During  these  later  changes  the  connection  between  the  superior  sagittal  sinus 
and  the  superior  cerebral  vein  is  lost  (Fig.  230).  The  middle  cerebral  vein 
becomes  the  superior  petrosal  sinus  which  forms  a  communication  between  the 
cavernous  sinus  and  transverse  sinus.  The  transverse  sinus  represents  the 
channel  between  the  superior  sagittal  sinus  and  the  cranial  end  of  the  cardinal 
vein;  or  in  other  words,  its  cranial  portion  represents  the  connection  between 
the  superior  sagittal  sinus  and  the  inferior  cerebral  vein  while  its  caudal  portion 


THE   DEVELOPMENT   OF  THE  VASCULAR   SYSTEM. 


255 


represents  the  inferior  cerebral  vein  itself  (Fig.  230,  compare  C  and  D). 
The  caudal  end  of  the  superior  sagittal  sinus  becomes  dilated  to  form  the  con- 
fluence of  the  sinuses  (confluens  sinuum) .  From  the  latter  a  new  vessel  grows 
out  to  form  the  straight  sinus,  and  a  further  growth  from  the  straight  sinus 
forms  the  large  vein  of  the  cerebrum  (vein  of  Galen).  The  inferior  sagittal 
sinus  also  represents  a  new  outgrowth  at  the  point  of  junction  of  the  large  vein 
of  the  cerebrum  and  inferior  sagittal  sinus  (Fig.  230,  D).  During  the  course  of 
development  the  lateral  vein  of  the  head  gradually  atrophies  and  finally  dis- 


.  caret,  vtiif      Suf>.  s&y. 
"Otic  vesicle 


Mid.,  cereb.  veiy      Coyfl.  of  sly  uses 
Otic  ve$tcl& 
Isif.ce.reb.  veiy 


L«.t.  veiy  o 


.  Cere6, 

Otic  vesicle    Midcereb.  vein 


Corjfl.or  sir)  uses 


Str.  sty  us 


e  veiy  ofcereb, 


c   .  .  ,  ,    — -  Sir/t/s  * 

5*A  «'•*"?  \Itf6et.9i?<,s  U 

fyt.ctrd.Kii?  \  Su^saj.SLrjus  Tr^\y.  sinus     Sub.  cereb.  m> 

Lot.  fe/^  <y*  ^<?arf  (/?/.  £«/•«*.  K««^ 

KFiG.  230. — Diagrams  representing  four  stages  in  the  development  of  the  veins  of  the 
head  in  human  embryos.     Mall. 

appears,  and  the  inferior  petrosal  sinus  probably  represents  a  new  formation  which 
extends  from  the  cavernous  sinus  to  the  transverse  sinus  (Fig.  230,  C  and  D). 
At  the  point  where  the  inferior  petrosal  joins  the  transverse  sinus  the  latter 
passes  out  of  the  skull  through  the  jugular  foramen  to  become  the  internal 
jugular  vein  (anterior  cardinal),  (Mall.) 

As   stated   in  a  preceding  paragraph,  the  anterior  cardinal  veins  extend 
from  the  ducts  of  Cuvier  to  the  head  region,  passing  to  the  dorsal  side  of  the 
branchial  arches.     They  are  at  first  paired  and  symmetrical,  but,  since  the 
17 


256 


TEXT-BOOK  OF  EMBRYOLOGY. 


heart  is  situated  in  the  cervical  region,  are  comparatively  short  and  receive 
blood  from  the  cervical  region  through  segmental  branches  which  belong  only 
to  the  most  cranial  of  the  cervical  segments.  The  other  segmental  cervical 
veins,  including  the  subclavian  veins,  open  at  first  into  the  posterior  cardinals 
(Fig.  231).  Later,  however,  as  the  heart  recedes  into  the  thorax  the  anterior 
cardinal  veins  are  elongated  and  the  segmental  cervical  veins,  including  the 
subclavians,  come  to  open  into  them  <Tig.  233).  The  bilateral  symmetry  is 


Ext.  jugular- 


Umbilical 


Omphalomesenteric 
(vitelline) 


Mesonephros 


Subcardinal 


Ant.  cardinal 
(int.  jugular) 


Duct  of  Cuvier 
•Subclavian 


Post,  cardinal 


•Iliac 


FIG.  231. — Diagram  of  the  venous  system  of  a  human  embryo  of  2.6  mm. 
Slightly  modified  from  Kollmann's  Atlas. 

then  broken  by  an  anastomosing  vessel  which  extends  obliquely  across  from  a 
point  on  the  left  cardinal  about  opposite  the  subclavian  to  a  point  nearer  the 
heart  on  the  right  subclavian  (Figs.  232,6,  and  233).  The  portion  of  the  left 
cardinal  cranial  to  the  subclavian  becomes  the  left  internal  jugular  vein  which 
communicates  with  the  intracranial  sinuses.  The  anastomosis  itself  becomes 
the  left  innominate  vein.  The  portion  of  the  left  cardinal  between  the  sub- 
clavian and  the  duct  of  Cuvier,  the  duct  of  Cuvier  itself,  and  the  left  horn  of  the 
snius  venosus  together  form  the  coronary  sinus  (Fig.  234).  On  the  right  side 


THE   DEVELOPMENT  OF  THE   VASCULAR   SYSTEM. 


257 


the  more  distal  part  of  the  cardinal  becomes  the  internal  jugular  vein;  the  por- 
tion between  the  subclavian  and  the  anastomosis  (left  innominate  vein)  becomes 
the  right  innominate  vein ;  and  the  common  stem  formed  by  the  latter  and  the 
left  innominate  constitutes  the  superior  vena  cava  which  opens  into  the  right 
atrium  (see  p.  231).  The  external  jugular  vein  on  each  side  appears  later  than 
the  superior  cardinal  as  an  independent  vessel  which  comes  to  lie  parallel  to  the 
internal  jugular  and  opens  into  it  near  the  subclavian.  The  opening,  however, 
shifts  to  the  subclavian,  where  it  is  usually  found  in  the  adult  (Figs.  233  and  234). 


Ant.  cardinal 


Duct  of  Cuvier 
Subclavian  -• 

Inf.  vena  cava 


Ant.  cardinal 
(int.  jugular) 


Post,  cardinal 
Subcardinal 


Iliac 


Iliac 


FIG.  232. — Diagrams  of  two  stages  in  the  development  of  the  anterior  and  posterior  cardinal  veins, 
the  subcardinal  veins  (revehent  veins  of  the  primitive  kidney),  and  the  inferior  vena  cava. 
The  small  branches  of  the  cardinals  and  subcardinals  ramify  in  the  primitive  kidneys 
(mesonephroi).  Slightly  modified  from  Hochstetter. 


The  changes  which  occur  in  the  posterior  cardinal  veins  are  very  extensive 
and  result  in  conditions  which  bear  but  little  resemblance  to  those  in  the  earlier 
stages.  In  connection  with  these  changes  the  development  of  the  inferior 
vena  cava  must  be  considered.  The  posterior  cardinal  veins  appear  very  early 
as  paired,  bilaterally  symmetrical  vessels  which  extend  from  the  duct  of  Cuvier 
to  the  tail  region  and  are  situated  ventro-lateral  to  the  aorta  (Fig.  231). 
From  the  first  they  receive  blood  from  the  body  wall  through  segmental  branches, 
and  as  the  primitive  kidneys  (mesonephroi)  develop  they  receive  blood  from 
them  also,  as  well  as  from  the  mesentery.  They  return  practically  all  the 
blood  from  the  region  of  the  body  situated  caudal  to  the  heart,  just  as  the 


258 


TEXT-BOOK  OF  EMBRYOLOGY. 


anterior  cardinals  return  the  blood  from  the  region  of  the  body  situated  cranial 
to  the  heart.  In  other  words,  the  two  sets  of  cardinal  veins  are  the  body 
veins  par  excellence  during  the  earlier  stages  of  development.  While  the  an- 
terior set  persists  for  the  most  part  as  permanent  vessels  and  increases  with  the 
development  of  the  body,  the  posterior  set  undergoes  regressive  changes,  its 
function  being  taken  by  a  new  vessel — the  inferior  vena  cava. 

Not  long  after  the  appearance  of  the  posterior  cardinals,  another  pair  of  longi- 
tudinal veins  appears  in  the  medial  part  of  the  mesonephroi.     They  increase 


Ext.  jugular  — 


Innominate  (right) 


Ant.  cardinal 
(int.  jugular) 


Subclavian 
Innominate  (left) 

Post,  cardinal 


Subcardinal 
(left  suprarenal) 


Ureter 


Iliac- 


FiG.  233. — Diagram  representing  a  stage  (later  than  Fig.  232)  in  the  development  of  the  superior 
vena  cava  and  the  inferior  vena  cava,  also  of  the  azygos  vein.     Hochstetter. 

in  size  as  the  mesonephroi  increase  and  receive  blood  from  the  latter.  They 
also  communicate  writh  the  cardinals  by  means  of  transverse  channels  which, 
however,  are  later  broken  up  as  the  mesonephroi  become  more  complicated  in 
structure.  These  vessels  are  known  as  the  subcardinal  veins,  or  revehent  veins 
of  the  primitive  kidneys  (Fig.  232,  A).  After  they  have  attained  a  considerable 
size,  a  large  anastomosis  is  formed  between  them  ventral  to  the  aorta  and  just 
caudal  to  the  omphalomesenteric  (superior  mesenteric)  artery  (Fig.  232,  B).  In 
the  meantime,  a  branch  of  the  ductus  venosus  (see  p.  263)  grows  caudally 
through  the  dorsal  part  of  the  liver  and  the  mesentery,  and  joins  the  right 


THE   DEVELOPMENT   OF  THE  VASCULAR  SYSTEM.  259 

subcardinal  vein  a  short  distance  cranial  to  the  above  mentioned  anastomosis 
(Fig.  232,  A  and  B).  This  branch  forms  the  proximal  part  of  the  inferior  vena 
cava.  At  the  same  time,  also,  each  subcardinal  forms  a  direct  connection  with 
the  corresponding  cardinal  at  a  point  opposite  the  first  anastomosis;  consequently 
the  inferior  vena  cava,  the  subcardinals  and  the  cardinals  are  all  in  direct 
communication  (Fig.  232,  B).  Thus  two  ways  are  formed  by  which  the 
blood  may  return  to  the  heart:  It  may  return  via' the  cardinals  and  ducts  of 
Cuvier,  and  via  the  inferior  vena  cava. 

It  is  obvious  that  while  these  conditions  exist,  that  is,  while  the  mesonephros  is  functional, 
and  blood  is  carried  to  it  by  the  cardinal  veins  and  from  it  by  the  subcardinal  veins,  there 
is  a  true  renal  portal  system.  The  blood  from  the  body  walls  and  lower  extremities  is  col- 
lected by  the  segmental  vessels  and  poured  into  the  cardinal  veins  and  is  then  distributed  in 
the  mesonephros  by  smaller  channels  or  sinusoids  (Minot),  whence  it  is  collected  and  carried 
off  by  the  subcardinal  veins.  This  passage  of  blood  through  purely  venous  channels  simu- 
lates the  conditions  in  the  liver  where  there  is  a  true  hepatic  portal  system. 

Int.  jugular 
(ant.  cardinal;  -  — -.--^  f   j["'"Sxt.  jugular 

Subclavian 

^•^H          ^•^^ff^' 
Innominate  (right)— 

^^^  \  i 

_  -Innominate  (left) 

Sup.  vena  cava" 

Coronary  sinus 


Azygos 

(post,  cardinal)"          ^  y  Accessory 

"hemiazygcs 


Hemiazygos 


FIG.  234. — Diagram  of  final  stage  in  the  development  of  the  superior  vena  cava 
and  the  azygos  vein.   (Compare  with  Fig.  233.) 

From  this  time  on,  the  changes  are  largely  regressions  in  the  cardinal  and 
subcardinal  systems,  corresponding  to  the  atrophy  of  the  mesonephroi,  and 
rapid  increase  in  the  vena  cava  and  its  branches.  The  cranial  end  of  each 
cardinal  becomes  smaller;  the  left  loses  its  connection  with  both  the  vena  cava 
and  the  duct  of  Cuvier,  the  right  its  connection  with  the  vena  cava  only  (Fig. 
234).  Subsequent  changes  in  these  parts  of  the  cardinals  will  be  considered 
in  the  following  paragraph.  For  a  time  the  caudal  ends  of  the  two  cardinals 
are  of  equal  importance.  Later,  however,  the  right  becomes  larger,  while  the 
left  atrophies.  The  right  thus  becomes  a  direct  continuation  and  really  a  part 
of  the  vena  cava  (Figs.  233  and  236).  This  is  brought  about,  of  course,  by  the 


260 


TEXT-BOOK  OF  EMBRYOLOGY. 


original  anastomosis  between  the  vena  cava  and  the  subcardinal  and  cardinal. 
On  the  left  side  the  anastomosis  persists  simply  as  the  proximal  part  of  the 
renal  vein  (Fig.  236);  on  the  right  side  the  renal  vein  is  a  new  structure  which 
develops  after  the  kidney  has  attained  practically  its  final  position,  and  opens 
into  the  vena  cava  secondarily.  The  inferior  vena  cava  itself  is  a  composite  vessel 
derived  from  four  different  anlagen.  i.  The  part  which  extends  from  the 
ductus  venosus  to  the  right  subcardinal  is  of  independent  origin.  2.  A  short 
portion  is  derived  from  a  part  of  the  right  subcardinal.  3.  Another  short  por- 
tion is  derived  from  the  cross-anastomosis  between  the  subcardinals  and 


Aorta 


Post,  cardinal  vein 


Mesonephric  duct       £"7T~~f"fl$ '•'?''•}  -y 


Omphalomesenteric  cartery       S; 


Dorsal  mesentery 
.Coelom 


Left  umbilical  vein 


FIG.  235. — From  a  transverse  section  of  a  5  mm.  human  embryo,  at  the  level  of  the 
Omphalomesenteric  (vitelline,  superior  mesenteric)  artery. 


cardinals.     4.  The  caudal  end  is  a  derivative  of  the  caudal  part  of  the  right 
cardinal  (compare  Figs.  232,  233,  236). 

Before  the  caudal  end  of  the  left  cardinal  vein  atrophies,  an  interesting  and 
important  change  occurs  in  the  relations  of  the  ureters  and  cardinals.  Pri- 
marily the  cardinal  veins  develop  to  the  ventral  side  of  the  ureters.  But  later 
a  collateral  of  each  cardinal  develops  to  the  dorsal  side  of  the  ureter.  These 
join  the  cardinal  cranial  and  caudal  to  the  ureter.  In  other  words,  a  venous 
loop  is  formed  around  the  ureter  (Fig.  233).  The  ventral  arm  of  the  loop  then 
atrophies  and  disappears,  leaving  the  dorsal  arm  as  the  direct  part  of  the  car- 
dinal vein.  On  the  right  side,  where  the  cardinal  persists  as  a  portion  of  the 


THE   DEVELOPMENT   OF  THE   VASCULAR   SYSTEM. 


261 


vena  cava,  the  latter  vessel  comes  to  lie  ventral  to  the  ureter  (Fig.  236,  A) .  On  the 
left  side  the  cardinal  atrophies,  leaving  only  the  portion  cranial  to  the  loop  as 
the  proximal  end  of  the  internal  spermatic  (testicular  or  ovarian)  vein  (Fig. 
236,  B).  Since  on  the  left  side  the  original  anastomosis  between  the  subcar- 
dinals  and  cardinals  persists  as  the  renal  vein,  the  left  internal  spermatic  is  a 
branch  of  the  renal.  The  right  internal  spermatic  vein  probably  represents  a 
branch  of  the  vena  cava  which  is  independent  of  the  cardinal. 


Inf.  vena  cava 


Suprarenal  gland    i-*\ 

Suprarenal  vein  (right) 

Renal  vein  (right)    — f" 

Int.  spermatic  (right) 


Inf.  vena  cava 
(right  post,  cardinal) 


Common  iliac  (right) 


Inf.  vena  cava 

,:\ Suprarenal  gland 

Suprarenal  vein  (left) 
»-j~ -  Kidney 

Renal  vein  (left) 

Int.  spermatic  "(left) 
(post,  cardinal) 

', Ureter 

Common  iliac  (left) 

Ext.  iliac 

— -  Int.  iliac 

?« — •*  Common  iliac  (right) 


FIG.  236.— Diagrams  representing  final  stages  in  the  development  of  the  inferior  vena  cava 
(compare  with  Fig.  233).     Slightly  modified  from  Hochstetter. 


Very  recent  investigations  (Huntington  and  McClure)  on  cat  embryos  have  shown  that 
the  venous  loop  around  the  ureter  is  much  more  extensive  than  in  some  other  Mammals. 
In  fact  the  dorsal  arm  of  the  loop,  to  which  the  name  supracardinal  vein  has  been  given, 
extends  from  the  iliac  vein  to  the  original  anastomosis  between  the  subcardinals  and  car- 
dinals. In  the  further  course  of  development  the  supracardinals  approach  each  other 
and  finally  fuse  in  the  medial  line,  forming  a  large  single  vessel  which  becomes  that  portion 
of  the  vena  cava  caudal  to  the  renal  veins.  In  this  event  both  cardinals,  which  form  the 
ventral  arms  of  the  venous  loops,  atrophy. 

Near  the  caudal  end  of  each  cardinal  vein  a  branch  arises  which  receives  the 
blood  from  the  corresponding  lower  extremity.  Then  a  transverse  anastomosis 
appears  between  the  two  cardinals  at  this  point  (Fig.  236,  A).  Since  the 
portion  of  the  left  cardinal  caudal  to  the  renal  vein  atrophies,  the  anastomosis 
itself  constitutes  the  left  common  iliac  vein  (Fig.  236,  B).  The  right  common 
iliac  is,  of  course,  the  original  branch  of  the  right  cardinal.  As  the  iliacs 
enlarge  they  form  the  two  great  branches  of  the  vena  cava. 


262 


TEXT-BOOK  OF  EMBRYOLOGY. 


With  the  atrophy  of  the  mesonephroi,  the  subcardinal  veins  diminish  in  size 
and  finally  disappear  for  the  greater  part.  The  part  of  the  right  subcardinal 
cranial  to  the  point  of  junction  with  the  vena  cava  disappears  entirely.  The 
portion  of  the  left  subcardinal  cranial  to  the  anastomosis  between  the  two  sub- 
cardinals  becomes  much  reduced  in  size,  but  persists  as  the  left  suprarenal  vein. 
The  left  suprarenal  vein  is  thus  a  branch  of  the  left  renal  vein,  since  the  latter 
represents  the  anastomosis  itself  (Figs.  232,  233,  236).  The  right  suprarenal 
vein  probably  does  not  represent  a  persistent  right  subcardinal,  but  is  a  new 
vessel  opening  into  the  vena  cava.  The  portion  of  each  subcardinal  caudal 
to  the  anastomosis  probably  disappears  entirely,  but  this  has  not  been  definitely 
determined. 

The  observations  on  the  development  of  the  azygos  veins  in  the  human 
embryo  are  only  fragmentary.  In  the  rabbit  the  portions  of  the  posterior  car- 


Duct  of  Cuviei— j« 


Right  umbilical  •-•{- 


Right  omphalomesenteric  "•••• 


Duct  of  Cuvier' 


_V._L. "Ductus  venosus 


...Left  umbilical 


•Left  omphalomesenteric 


FIG.  237. — Diagrams  illustrating  two  stages  in  the  transformation  of  the  omphalomesenteric 
and  umbilical  veins  in  the  liver.     Hochstetter. 

dinal  veins  immediately  cranial  to  the  anastomosis  between  the  subcardinals 
and  cardinals,  that  is,  just  cranial  to  the  renal  veins,  disappear.  The  more 
cranial  portion  of  the  right  cardinal  persists  as  the  azygos  vein  which  receives 
the  intercostal  (segmental)  branches  and  opens  into  the  superior  vena  cava. 
An  oblique  anastomosis  is  formed,  dorsal  to  the  aorta,  between  the  two  cardinals 
(Fig.  233).  This  anastomosis  and  the  portion  of  the  left  cardinal  caudal  to  it 
together  form  the  hemiazygos  vein.  The  portion  of  the  left  cardinal  cranial 
to  the  anastomosis  loses  its  connection  with  the  duct  of  Cuvier  (or  coronary 
sinus)  and  becomes  the  accessory  hemiazygos  vein  (Fig.  234).  The  ascending 
lumbar  veins,  which  join  the  azygos  and  hemiazygos,  probably  do  not  represent 
persistent  parts  of  the  caudal  ends  of  the  cardinals,  but  are  formed  by  longi- 
tudinal anastomoses  between  the  original  segmental  lumbar  veins. 

The  changes  which  occur  in  the  region  of  the  liver  are  of  much  importance 
and  result  in  conditions  which  bear  no  resemblance  to  the  primary  ones.     As 


THE   DEVELOPMENT  OF  THE  VASCULAR   SYSTEM. 


263 


has  already  been  noted,  the  omphalomesenteric  veins  enter  the  body  at  the 
umbilicus,  pass  cranially  along  the  intestine  and  open  into  the  caudal  end  of  the 
heart.  The  umbilical  veins,  which  appear  soon  after,  enter  the  body  at  the 
umbilicus  and  pass  cranially,  one  on  each  side,  in  the  ventro-lateral  part  of  the 
body  wall;  at  the  level  of  the  heart  they  turn  mesially  through  the  septum  trans- 
versum  and  join  the  corresponding  omphalomesenteric  veins  to  form  a  common 
trunk  on  each  side,  into  which  the  duct  of  Cuvier  then  opens  (Fig.  231). 
When  the  liver  grows  out  as  an  evagination  from  the  intestine,  it  comes  in  con- 
tact with  the  proximal  ends  of  the  omphalomesenteric  veins  and,  as  it  enlarges, 
breaks  them  up  into  numerous  smaller  channels  (Fig.  237). 


(Esophagus 


Ant.  cardinal 


Post,  cardinal 

Liver 
Right  umbilical 

Venous  ring 
Venous  ring 


Duct  of  Cuvier 
Left  umbilical 
Ductus  venosus 


Left  umbilical 


Omphalomesenteric 
Intestine 


FIG.  238. — Veins  in  the  liver  region  of  a  human  embryo  of  4  mm.     His,  Kollmann's  Atlas. 

The  blood  then,  instead  of  having  a  direct  channel,  is  forced  to  flow  through 
these  smaller  channels  which  have  been  termed  sinusoids.  When  the  liver  has 
attained  a  considerable  size  a  more  direct  and  definite  channel  is  formed, 
which  extends  through  the  substance  of  the  liver  from  the  proximal  end  of  the 
right  omphalomesenteric  vein  obliquely  caudally  to  the  left  omphalomesenteric 
vein.  This  newly  formed  channel  is  the  ductus  venosus  (Figs.  237  and  238). 
In  the  meantime,  three  transverse  anastomoses  develop  between  the  omphalo- 
mesenteric veins  just  caudal  to  the  liver.  The  middle  one  is  dorsal  to  the 
intestine,  the  other  two  ventral,  so  that  the  intestine  is  surrounded  by  two  venous 
loops  or  rings  (Figs.  237  and  238).  At  the  same  time  a  cross-anastomosis 
develops  between  the  left  umbilical  vein,  which  is  primarily  the  smaller,  and 


264 


TEXT-BOOK  OF  EMBRYOLOGY. 


the  corresponding  omphalomesenteric.  This  anastomosis  joins  the  omphalo- 
mesenteric  at  about  the  point  where  the  latter  joins  the  ductus  venosus,  so 
that  it  seems  to  be  a  continuation  of  the  ductus  venosus.  A  similar  cross-anasto- 
mosis also  develops  between  the  right  umbilical  and  right  omphalomesenteric 
(Figs.  237  and  238).  Thus  the  blood  that  is  brought  in  from  the  placenta  by 
the  umbilical  veins  may  pass  through  the  liver.  Then  the  portion  of  each 
umbilical  between  the  anastomosis  and  the  duct  of  Cuvier  atrophies  and  disap- 


Sinus  venosus  and 
orifice  of  ductus  venosus 


Revehent  hepatic 


Advehent  hepatic 


Right  umbilical 


Omphalomesenteric 
(portal) 


Umbilical  vein 


Revehent  hepatic 


Advehent  hepatic 


Left  umbilical 


Umbilical  cord 


FIG.  239. — Veins  in  the  liver  region  of  a  human  embryo  of  10  mm.     Kollmann's  Atlas. 

pears  (Fig.  238).  The  remaining  portion  of  the  left  umbilical,  which  was 
originally  the  smaller,  gradually  increases  in  size  and  finally  carries  all  the 
blood  from  the  placenta.  The  right  umbilical,  on  the  other  hand,  loses  its 
connection  with  the  liver  and  persists  only  as  a  small  vein  in  the  body  wall, 
which  opens  into  the  left  umbilical  vein  near  the  umbilical  cord  (Fig.  239). 
Thus  there  is  the  peculiar  phenomenon  of  a  vessel  carrying  blood  in  different 
directions  at  different  periods  of  its  history.  During  the  course  of  develop- 
ment of  the  septum  transversum  and  diaphragm  the  left  umbilical  is  withdrawn 


THE   DEVELOPMENT  OF  THE  VASCULAR   SYSTEM. 


from  the  body  wall  and  passes  directly  from  the  umbilicus  to  the  ventral  side  of 
the  liver.  During  foetal  life  it  conveys  all  the  blood  from  the  placenta  to  the 
liver.  A  part  of  the  blood  is  distributed  in  the  liver,  a  part  is  carried  directly 
to  the  inferior  vena  cava  by  the  ductus  venosus  (Fig.  240).  After  birth  the 
placental  blood  is  cut  off  and  the  umbilical  vein  degenerates  to  form  the  round 
ligament  of  the  liver. 

The  venous  rings  around  the  intestine  also  undergo  marked  changes.     The 


Heart 


Inf.  vena  cava ~ 


Ductus  venosus  - 


Left  lobe  of  liver— 


Umbilical  vein 


Umbilical  ring 


Hepatic  veins 


Rightlobe  of  liver 


Gall  bladder 


-  -  Portal  vein 

(omphalomesenteric) 


Intestine 


Inf.  vena  cava 


FIG.  240. — Veins  of  the  liver  (seen  from  below)  of  a  human  foetus  at  term.     Kollmann's  Atlas. 

right  side  of  the  most  caudal  and  the  left  side  of  the  most  cranial  disappear;  the 
remaining  vessel  finally  loses  its  connection  with  the  ductus  venosus  and  becomes 
the  portal  vein  (Figs.  237,  238,  239  and  240).  The  portal  vein  is  thus  a  deriva- 
tive of  the  omphalomesenterics.  After  birth,  when  the  placental  blood  is 
cut  off,  blood  is  distributed  in  the  liver  by  branches  of  the  portal  vein,  which 
represent  the  advehent  hepatic  veins;  it  is  collected  again  by  branches  which 
unite  to  form  the  revehent  hepatic  veins,  or  hepatic  veins  proper,  and  the  latter 


266 


TEXT-BOOK  OF  EMBRYOLOGY. 


Aijt.  ca.rJL.  vtij 


open  into  the  inferior  vena  cava.  The  advehent  and  revehent  hepatic  veins  are 
formed  by  the  enlargement  of  some  of  the  original  sinusoids  (Figs.  237  and  239). 
Observations  on  the  development  of  the  veins  in  the  extremities  of  human 
embryos  are  so  fragmentary  that  it  seems  advisable  to  make  use  of  the  work 
that  has  been  done  on  the  rabbit.*  In  the  upper  extremity  the  first  vein  to 
develop  is  the  primary  ulnar  vein  which  begins  in  the  radial  (cranial)  side  of 
the  extremity  near  its  proximal  end,  extends  distally  along  the  radial  border, 
thence  proximally  along  the  ulnar  (caudal)  border,  and  opens  into  the 
anterior  cardinal  vein  (internal  jugular)  near  the  duct  of  Cuvier  (Fig.  241). 
This  condition  is  present  in  rabbit  embryos  of  thirteen  days.  A  little  later  a 
second  vessel,  the  cephalic  vein,  appears  as  a  branch  of  the  external  jugular, 

extends  along  the  radial  side  of  the  extremity  and 
becomes  connected  with  the  digital  veins  (Fig.  242). 
When  the  digital  veins  are  taken  up  by  the  cephalic, 
the  distal  portion  of  the  primitive  ulnar  undergoes 
regression.  These  changes  have  taken  place  in 
rabbit  embryos  of  fifteen  days,  and  for  a  short 
period  the  cephalic  vein  is  the  chief  vessel  of  the 
extremity.  The  primitive  ulnar  vein,  however, 
develops  more  rapidly  than  the  cephalic  and,  with 
its  branches,  soon  becomes  the  chief  vessel;  the 
portion  in  the  forearm  gives  rise  to  either  the  ulnar 
°r  basilic  vein;  the  portion  in  the  arm  becomes  the 
brachial  vein  which  then  passes  over  into  the  axillary, 
and  the  latter  in  turn  passes  over  into  the  sub- 
clavian.  The  cephalic  vein  of  the  embryo  persists  as  the  cephalic  of  the 
adult,  and,  during  the  period  when  it  forms  the  chief  vessel  of  the  extremity,  a 
branch  arises  from  it  which  becomes  the  radial  vein.  Primarily  the  cephalic 
vein  opens  into  the  external  jugular,  but  later  a  new  connection  is  formed 
with  the  axillary,  while  the  original  connection  persists  as  the  jugulocephalic 
(Fig.  243). 

In  a  rabbit  embryo  of  ten  and  one-half  days  a  vein  follows  the  border  of  the 
lower  extremity  all  the  way  round,  connecting  on  the  cranial  side  with  the  um- 
bilical and  on  the  caudal  side  with  the  posterior  cardinal.  This  is  the  primitive 
jibular  vein,  and  from  its  course  is  homologous  with  the  primitive  ulnar  vein  of 
the  upper  extremity  (Fig.  241).  From  this  time  on,  however,  the  course  of  de- 
velopment in  the  lower  extremity  differs  from  that  in  the  upper.  The  connection 
of  the  fibular  vein  with  the  umbilical  is  soon  lost.  In  older  embryos  (fifteen 
days)  two  branches  of  the  fibular  vein  have  appeared;  one  of  these,  the  anterior 
tibial  vein,  begins  on  the  dorsum  of  the  foot  and  extends  diagonally  proximally,  to 

*  Lewis,  F.  T  ,  see  "  References  for  Further  Study,"  (p.  292). 


F7n  SSS  rfT,S 

embryo  of  14  days  (n  mm.), 
Modified  from  Lewis. 


THE  DEVELOPMENT  OF  THE   VASCULAR  SYSTEM. 


267 


open  into  the  fibular  in  the  caudal  border;  the  other,  the  so-called  connecting 
branch,  begins  as  twigs  in  the  abdominal  wall  and  tibial  side  of  the  extremity  and 
opens  into  the  fibular  just  proximal  to  the  opening  of  the  anterior  tibial  (Fig.  242). 
Later  the  distal  part  of  the  primitive  fibular  is  broken  up  by  the  differentiation 
of  the  digits  (toes)  and  disappears  almost  up  to  the  point  of  junction  with  the 
anterior  tibial.  The  latter  enlarges  and  receives  the  digital  branches,  and 
appears  as  a  continuation  of  the  proximal  part  of  the  primitive  fibular.  The 
anterior  tibial  and  primitive  fibular  together  thus  constitute  the  sciatic  vein 
(Fig.  243).  Another  vessel  appears  in  embryos  of  fifteen  days,  which  represents 
the  beginning  of  the  femoral  vein  and  opens  into  the  cardinal,  cranial  to  the 


Ext.jUJUUr  nif-^jLiftft  yel\ 


veirj 


FlG.   242. 


FIG.  243. 


FIG.  242. — Diagram  of  the  veins  in  the  extremities  of  a  rabbit  embryo  of  14  days 

and  18  hours  (14.5  mm.).     Modified  from  Lewis. 

FIG.  243. — Diagram  of  the  veins  in  the  extremities  of  a  rabbit  embryo  of  17  days 
(21  mm.).     Modified  from  Lewis. 


opening  of  the  sciatic  (Fig.  243).  From  this  time  on  the  femoral,  with  its 
branches,  enlarges  at  the  expense  of  the  other  veins  and  becomes  the  principal 
vein  of  the  lower  extremity.  In  the  human  embryo  the  femoral  anastomoses 
with  the  sciatic  near  the  knee  and  the  proximal  portion  of  the  sciatic  then 
atrophies,  the  distal 'portion  persisting  as  the  small  saphenous  vein.  The  large 
saphenous  vein  and  the  posterior  tibial  vein  possibly  are  derivatives  of  the 
femoral,  but  this  question  has  not  been  settled. 

CHANGES  IN  THE  CIRCULATION  AT  BIRTH. — During  fcetal  life  the  course  of 
the  blood  is  adapted  to  the  placental  circulation,  since  the  placenta  is  the  only 
means  by  which  the  blood  is  purified  and  from  which  the  foetus  derives  its 
nutriment.  The  pure  blood  from  the  placenta  passes  through  the  umbilical 
vein  to  the  liver;  there  a  part  of  it  is  distributed  to  the  liver  by  some  of  the 


268  TEXT-BOOK  OF  EMBRYOLOGY. 

advehent  veins,  is  collected  again  by  the  revehent  veins  and  poured  into  the 
inferior  vena  cava;  a  part  passes  directly  to  the  vena  cava  through  the  ductus 
venosus.  At  this  point  the  blood  acquires  some  impurity  from  the  stream 
brought  in  by  the  vena  cava  itself  and  the  portal  vein.  The  slightly  impure 
blood  then  flows  into  the  right  atrium,  is  directed  by  the  Eustachian  valve 
through  the  foramen  ovale  into  the  left  atrium,  thence  flows  into  the  left  ven- 
tricle and  is  forced  out  into  the  aorta.  A  part  of  the  blood  flows  on  through  the 
aorta,  a  part  is  carried  to  the  upper  extremities  and  head  and  neck  regions  by  the 


Sup.  vena  cava 
Lungs 

Right  atrium 

Right  ventricle 

Inf.  vena  cava 

Liver 

Ductus  venosus 

Placenta 

Inf.  vena  cava 

Umbilical  vein 
Umbilical  artery 


Ant.  part  of  body 

Carotid  and 
subclavian  arteries 

Ductus  arteriosus 

Pulmonary  artery 
Left  ventricle 


Post,  part  of  body 


FIG.  244. — Diagram  illustrating  the  foetal  circulation.     Compare  with  Fig.  245. 

Modified  from  Kottmann. 

The  shading  represents  the  relative  impurity  of  the  blood  in  different  regions,  the 
darkest  shading  representing  the  most  impure  blood. 


subclavian  and  carotid  arteries.  The  latter  part,  then  becoming  impure,  is 
carried  back  to  the  right  atrium  by  the  subclavian  and  jugular  veins  and  superior 
vena  cava;  from  the  right  atrium  the  greater  portion  flows  into  the  right  ventricle 
and  thence  is  forced  out  into  the  large  pulmonary  artery.  But  since  the  lungs 
are  non-functional,  this  blood  passes  through  the  ductus  arteriosus  to  join  the 
stream  in  the  aorta.  The  blood  received  by  the  more  cranial  portion  of  the 
foetus  is  but  slightly  impure,  for  the  impure  blood  from  the  ductus  arteriosus 
joins  the  aortic  stream  distal  to  the  origin  of  the  subclavian  and  carotid  arteries. 
This  accounts  for  the  fact  that  the  more  cranial  portion  of  the  body  generally 


THE   DEVELOPMENT  OF  THE  VASCULAR  SYSTEM. 


269 


is  better  developed  than  the  more  caudal  portion.  It  is  well  to  note  here 
that  the  liver  receives  purer  blood  than  any  other  part  of  the  body,  and  this  is 
undoubtedly  correlated  with  the  relatively  enormous  size  of  that  organ  in  the 
foetus.  The  rather  impure  blood  which  starts  through  the  dorsal  aorta  is  in 
part  distributed  to  the  viscera,  body  walls,  and  lower  extremities  by  the  visceral 
and  segmental  arteries,  and  thence  is  collected  by  the  branches  of  the  portal 
vein  and  inferior  vena  cava  to  be  returned  as  impure  blood  to  the  umbilical 
current  at  the  liver;  in  part  it  is  carried  by  the  umbilical  arteries  to  the  placenta, 
there  to  be  purified  and  collected  by  the  branches  of  the  umbilical  vein  (see 
Fig.  244). 


Sup.  vena  cava 
Lungs 

Pulmonary  veins 
Right  atrium 

Right  ventricle 
Inf.  vena  cava 

Hepatic  vein 
Liver 

Inf.  vena  cava 


Ant.  part  of  body 


Carotid  and 
subclavian  arteries 


Pulmonary  artery 


•Left  ventricle 


Hepatic  artery 


•Post,  part  of  body 


FIG.  245. — Diagram  illustrating  the  circulation  in  the  adult.     Compare  with  Fig.  244.     The 
shading  represents  the  relative  impurity  of  the  blood,  the  white  being  the  purest  blood. 

At  birth,  when  the  placental  circulation  is  cut  off,  the  proximal  end  of  the 
umbilical  vein  atrophies  to  form  the  round  ligament  of  the  liver;  the  ductus 
venosus  also  atrophies  and  becomes  merely  a  connective-tissue  cord  in  the  liver. 
The  hepatic  portal  circulation  is  still  maintained  by  the  portal  vein.  The 
foramen  ovale  is  closed  and  the  impure  blood  from  the  inferior  vena  cava,  as 
well  as  that  from  the  superior,  passes  from  the  right  atrium  into  the  right 
ventricle  and  thence  is  forced  out  through  the  pulmonary  artery  to  the  lungs, 


270 


TEXT-BOOK  OF  EMBRYOLOGY. 


which  at  this  time  become  functional,  and  is  returned  to  the  left  atrium  by  the 
pulmonary  veins.  The  ductus  arteriosus  atrophies  to  form  the  ligamentum 
arteriosum.  From  the  left  atrium  the  pure  blood  flows  into  the  left  ventricle, 
thence  is  forced  out  through  the  aorta  and  its  branches  to  all  parts  of  the  body. 
At  the  same  time  the  more  distal  portions  of  the  umbilical  arteries  in  the  em- 
bryo atrophy  to  form  the  lateral  umbilical  ligaments,  their  proximal  portions 
persisting  as  the  superior  vesical  arteries  (see  Fig.  245). 

Histogenesis  of  the  Blood  Cells. 

There  is  probably  no  other  subject  in  embryology  about  which  there  are 
more  conflicting  views  than  the  problem  of  the  origin  and  histogenesis  of  the 
blood  cells.  The  problem  concerns  not  only  the  first  blood  cells  in  the  embryo 
and  their  life  history,  but  also  the  origin  and  development  of  new  cells  during 


Entoderm 
Endothelium 


Blood  vessel  with 
normoblasts 


Mesoderm 


FlG.  246. — From  section  of  wall  of  yolk  sac  of  a  human  embryo  of  5  mm.,  showing  blood 
vessel  containing  nucleated  red  blood  cells  (normoblasts).       Photograph. 

later  fcetal  and  postnatal  life  of  the  individual.  While  in  some  respects  much 
light  has  been  thrown  on  the  subject,  by  studies  on  pathological  blood  condi- 
tions such  as  anaemia,  leucocytosis,  leukaemia,  and  other  conditions  accompanied 
by  changes  in  the  blood  and  disturbances  in  the  blood-forming  organs,  the 
problem  has  in  other  respects  been  complicated  by  these  same  studies.  Obvi- 
ously the  questions  of  the  embryonic  origin  of  the  blood  cells,  of  their  normal 
origin  during  postnatal  life,  and  their  origin  in  abnormal  or  pathological  con- 
ditions are  closely  associated. 

The  latest  theory  of  the  development  of  the  blood  cells  is  the  result  of  an 
extensive   series   of   investigations   by   Maximow,   with   whom   Weidenreich, 


THE  DEVELOPMENT  OF  THE  VASCULAR  SYSTEM. 


271 


Dantschakoff,  and  to  a  large  extent,  Saxer,  Ruckert,  and  Mollier  are  in  agree- 
ment. The  theory  in  question  is  that  all  blood  cells  have  a  common  stem  and 
that  this  stem  is  represented  by  cells  derived  from  the  mesenchyme,  the  entoder- 
mal  origin  of  any  of  the  cells  being  denied. 

Maximow's  views  are  briefly  outlined  as  follows:  The  sites  of  blood  forma- 
tion are  (i)  blood  islands  in  the  area  opaca  and  (2)  mesenchyme  in  general, 
especially  the  mesenchyme  of  the  liver,  marrow  and  lymphoid  organs.  In 
adult  life  all  kinds  of  blood  cells  arise  in  marrow,  chiefly  lymphocytes  in  lymphoid 
organs,  and  possibly  wandering  cells  in  the  connective  tissues. 

In  the  formation  of  the  blood  islands  in  the  area,  opaca,  the  mesenchymal 
cells  become  arranged  in  strands.  The  central  cells  of  the  strands  become 
free  and  rounded,  the  peripheral  cells 
lengthen  and  form  endothelium.  Both 
types  are  thus  mesenchymal  deriva- 
tives. Endothelial  cells  may  free 
themselves  from  the  vessel  wall  and 
join  the  central  cells,  or  may  break 
away  from  the  outside  and  join  the 
genera  mass  of  mesenchyme.  These 
observations  have  led  to  the  conclu- 
sion that  endothelium  is  not  a  specific 
tissue  but  rather  a  modification  of 
mesenchyme. 

The  central  cells  of  the  blood 
islands,  known  as  primitive  blood 
cells,  are  spherical  in  shape,  smooth, 
and  are  from  10  to  12.5  microns  in 
diameter.  They  contain  large  vesic- 
ular nuclei  with  very  fine  chromatin  granules;  the  nucleoli  are  large  and 
irregular.  Mitotic  figures  are  frequently  seen.  The  cytoplasm  forms  a  narrow 
rim  around  each  nucleus,  is  finely  reticulated  and  contains  vacuoles,  attraction 
spheres  and  centrioles,  but  no  hsemoglobin.  Cells  of  this  character  are  found 
in  rabbit  embryos  up  to  nine  and  one-half  days. 

Following  this  stage,  the  primitive  blood  cells  give  rise  to  two  types  of  cells, 
lymphocytes  and  primitive  erythroblasts.  The  former  constitute  a  minority  of 
the  descendants  of  the  primitive  blood  cells  and  resemble  the  large  lymphocytes 
of  the  adult.  The  nucleus  is  relatively  large,  slightly  indented,  and  somewhat 
excentric.  The  cytoplasm  surrounds  the  nucleus  as  a  rim,  is  markedly  baso- 
phile,  contains  vacuoles  and  an  attraction  sphere,  and  shows  small  pseudopodia. 
These  cells  are  from  6.5  to  13  microns  in  diameter.  The  primitive  erythroblasts 
are  sharply  circumscribed  spheres,  about  the  size  of  the  primitive  blood  cells. 

18 


FlG.  247. — From  section  of  liver  of  a  27  mm. 
cat  embryo,  showing  erythroblasts  in  blood 
vessels.  In  the  upper  right  hand  corner  of 
the  figure  is  a  group  of  non-nucleated  red 
blood  cells  (erythrocytes).  HowelL 


272 


TEXT-BOOK  OF  EMBRYOLOGY. 


FIG.  248. — Nucleated  red  blood 
cells  from  marrow  of  young 
kitten  after  bleeding.  Howell. 

The  upper  part  of  the  figure 
shows  mitosis  in  nucleated  red 
cells;  the  lower  part  shows  the 
condensation  of  the  chromatin. 


The  nucleus  is  relatively  smaller,  round  or  oval,  and  contains  more  distinct 
chromatin  granules  and  more  prominent  nucleoli.  The  cytoplasm  contains  a 
trace  of  haemoglobin  and  looks  homogeneous.  Mitoses  are  frequent. 

In  the  further  development  of  the  primitive 
erythroblasts,  their  nuclei  become  smaller,  the 
chromatin  paler,  and  the  nuc  eoli  less  distinct. 
The  nuclei  either  distintegrate  in  the  cells  or  are 
extruded,  the  cells  thus  losing  their  ability  to 
multiply.  The  cytoplasm  in  the  meantime  in- 
creases in  amount,  the  outlines  becoming  slightly 
irregular,  and  acquires  an  abundance  of  haemo- 
globin. This  type  of  cell  then  declines  and  is 
ingested  by  phagocytes  derived  from  the  vessel 
wall,  thus  perishing  without  descendant.  The 
primitive  erythroblasts  and  their  derivatives 
constitute  but  a  short  lived  race  of  oxygen 
carriers. 

The  new  race  of  red  blood  cells,  representing  the  type  which  lasts  through- 
out the  life  of  the  organism,  is  derived  from  lymphocytes.  Some  of  the  lymph- 
ocytes, the  characters  of  which  have  been  mentioned  in  a  preceding  paragraph, 
become  modified  in  that  the  cytoplasm  becomes  less  basophilic,  loses  its  vacu- 
oles  and  acquires  a  trace  of  haemoglobin; 
the  nuclei  become  excentric,  the  chro- 
matin denser,  and  the  nucleoli  less  con- 
spicuous. These  modified  cells,  to  which 
the  term  megaloblasts  is  applied,  lie  in 
groups  all  the  members  of  which  present 
about  the  same  stage  of  differentiation, 
and  measure  from  8  to  9  microns  n 
diameter. 

The  megaloblasts  in  turn  give  rise  to 
other  eel's  by  mitosis,  general  reduction 
in  size,  increase  in  haemoglobin,  increas- 
ing density  of  nuclei,  and  loss  of  nucleoli. 
These  new  cells  are  called  normoblasts 
(Fig.  246).  From  these  the  nuclei  are 
extruded  (beginning  at  the  thirteenth  or 
fourteenth  day  in  the  rabbit),  resulting 
in  the  definitive  red  blood  cell  or  erythrocyte  (Fig.  249). 

Thus,  in  the  manner  described,  red  blood  cells  are  being  constantly  differ- 
entiated from  lymphocytes,  which  in  turn  are  derived  from  mesenchyme  cells. 


FIG.  249. — Showing  the  escape  of  the  nuclei 
from  nucleated  red  blood  cells.  Howell. 

l,  2,  3,  4,  represent  stages  of  extrusion 
observed  in  living  cells;  a,  from  circulat- 
ing blood  of  adult  cat  after  bleeding  four 
times;  b,  from  young  kitten  after  bleed- 
ing; c,  from  90  mm.  cat  embryo;  others 
from  marrow  of  adult  cat. 


THE  DEVELOPMENT  OF  THE  VASCULAR  SYSTEM.  273 

The  process  goes  on  not  only  in  the  area  vasculosa  of  the  embryo  but  also  in  the 
mesenchyme  in  general  in  the  body,  especially  in  the  liver  in  the  young  embryo 
(Fig.  247),  and  in  the  bone  marrow  in  later  embryonic  life  and  postnatal  life 
(Fig.  248).  Organs  or  tissues  in  which  blood-cell  formation  occurs  are  spoken 
of  as  performing  a  hcematopoietic  function. 

Erythrocytes 


•  Megakaryocyte 


/ 


w 


V--.     Mp*»e Fat  space 

X  l"-Tr.  Megaloblasts 


V"' 

Leucocytes  Reticulum 

FIG.  250. — Section  of  red  bone  marrow  from  rabbit's  femur. 

The  descent  of  lymphocytes  and  red  blood  cells  may  be  graphically  repre- 
sented in  the  following  manner: 

Primitive  blood  cells 
Derived  from  mesenchyme 

/  \ 

Lymphocytes  Primitive  erythroblasts 

/  \  I 

/  Megaloblasts  Primitive  erythrocytes 

/  This  type  disappears 

Lymphocytes  Normoblasts 

/  \  I 

/      Megaloblasts     Erythrocytes 

etc. 

Normoblasts 

Erythrocytes 


274 


TEXT-BOOK  OF  EMBRYOLOGY. 


In  the  human  embryo  (he  first  non-nucleated  disks  or  definitive  erythrocytes 
appear  in  the  blood  stream  during  the  second  month.  From  this  time  on,  the 
number  gradually  increases  with  a  concomitant  reduction  in  the  number  of 
nucleated  forms.  At  the  time  of  birth,  under  normal  conditions,  the  non- 
rifUcleated  disks  constitute  the  only  form  of  red  blood  cell  found  in  the  general 
circulation. 

Since  the  erythrocytes  are  constantly  dis'ntegrating  and  disappearing  during 
the  life  of  the  individual,  there  must  be  some  means  of  replacing  them.  Ac- 
cording to  the  theory  of  Maximow,  a  new  supply  is  being  constantly  derived  from 
lymphocytes.  Under  normal  conditions  this  process  goes  on  for  the  most  part, 


FIG.  251. — From  section  of  groin  of  human  embryo  of  about  7  weeks.     Gulland. 
c.  t.  n.,  Connective  (mesenchymal)  tissue  nuclei;  ly.,  lymphatic  vessel;  tr.,  trabecula  or  strand  of 
mesenchymal  tissue  between  two  lymphatic  vessels;  iv.  /.,  wandering  leucocytes  (according 
to  Gulland,  identical  with  first  lymphocytes). 

probably  wholly,  in  the  bone  marrow.  Indifferent  mesenchyme  cells  in  the 
marrow  become  differentiated  into  lymphocytes,  some  of  which  in  turn  give  rise 
to  megaloblasts,  normoblasts  and  erythrocytes  in  order,  as  described  in  the  pre- 
ceding paragraphs.  In  this  way  new  erythrocytes  are  being  constantly  added 
to  the  blood  as  the  old  ones  perish,  and  an  equilibrium  is  thus  maintained. 

The  question  of  the  origin  of  the  leucocytes  is  even  more  difficult  than  that 
of  the  origin  of  the  red  blood  cells.  One  view,  of  which  Gulland  has  been  the 
strongest  advocate,  is  that  the  lymphocytes,  which  are  differentiated  mesenchyme 
cells  (Fig.  251),  represent  the  progenitors  of  the  other  varieties  of  white  blood 
cells,  or  in  other  words  represent  the  youngest  variety  of  leucocyte.  According 
to  this  view,  the  lymphocytes  give  rise  to  cells  with  a  rather  large  amount  of 


THE  DEVELOPMENT  OF  THE  VASCULAR  SYSTEM.  275 

finely  granular  cytoplasm — mononuclear  leucocytes;  the  nuclei  of  the  mononu- 
clear  forms  become  drawn  out  into  horse-shoe  shapes  characteristic  of  the  transi- 
tional variety;  the  nuclei  of  the  transitional  forms  then  become  lobed  or  separated 
into  two  or  more  parts  to  form  the  nuclei  of  the  polymorphonuclear  or  poly- 
nuclear  varieties.  In  this  case,  therefore,  the  different  varieties  of  leucocytes 
bear  definite  genetic  relations  to  one  another,  the  polymorphonuclear  and 
polynuclear  forms  indicating  senility  and  the  beginning  of  degeneration. 

The  more  recent  studies  on  the  formation  of  blood  cells  (Maximow  and 
others)  have  to  a  considerable  extent  discredited  the  view  that  the  different 
varities  of  white  blood  cells,  from  lymphocytes  to  polynuclear  forms,  bear 
definite  genetic  relations  to  one  another.  While  they  are  all  derived  from  in- 
different mesenchyme  cells,  yet  they  do  not  fall  into  a  series  each  member  of 
which  bears  a  direct  genetic  relation  to  the  preceding  and  succeeding  member, 
as  Gulland  maintained  (see  preceding  paragraph).  Maximow  has  demon- 
strated the  origin  of  lymphocytes  not  only  in  the  area  vasculosa  but  also  on 
the  body  mesenchyme.  He  holds,  furthermore,  that  the  granular  forms  of 
leucocytes  arise  only  in  the  body  mesenchyme. 

In  the  bone  marrow  the  indifferent  mesenchyme  cells  may  give  r'se  to 
several  different  kinds  of  cells.  They  may  differentiate  into  osteoblasts,  which 
by  fusion  produce  osteoclasts  (polykaryocytes) .  As  already  stated,  they  may 
become  modified  to  form  lymphocytes  which  in  turn  may  give  rise  to  red  blood 
cells.  They  may  produce  the  various  members  of  the  myelocyte  series  and 
leucocytes  of  all  varieties.  The  genetic  relations  of  myelocytes  and  leucocytes 
have  not  been  clearly  made  out.  From  the  mesenchyme  cell  may  be  derived 
also  the  type  of  cell  known  as  the  megakaryocyte,  from  which,  according  to 
Wright,  the  blood  plates  are  broken  off  (see  below).  (Fig.  250.) 

What  part  is  played  by  the  lymphoid  organs  in  the  production  of  the  different 
kinds  of  white  blood  cells  is  a  matter  of  some  doubt.  It  is  certain,  however, 
that  lymphocytes  multiply  in  these  organs,  especially  in  the  germinal  centers  in 
the  lymph  glands,  and  it  is  very  probable  that  they  differentiate  in  situ  out  of 
mesenchyme  cells  in  the  developing  lymph  glands  (see  p.  280).  At  one  time 
Beard  attempted  to  discredit  the  mesenchymal  origin  of  leucocytes  by  his 
studies  on  the  thymus  in  lower  vertebrates.  -He  asserted  that  he  found  no 
leucocytes  in  the  blood  before  the  appearance  of  the  thymus,  and  that  the 
primitive  leucocytes  were  apparently  derived  from  the  epithelial  (entodermal) 
cells  which  constitute  the  anlage  of  the  thymus.  The  recent  researches  of 
Maximow  have  disproved  Beard's  theory. 

The  origin  of  the  blood  plates  is  even  more  obscure  than  the  origin  of  the 
blood  cells,  i.  The  theory  that  they  represent  products  of  disintegration  of 
leucocytes  has  not  been  corroborated.  2.  The  view  that  the  plates  stand  in 
genetic  relation  to  the  erythrocytes  is  supported  by  the  fact  that  the  latter  can 


276 


TEXT-BOOK  OF  EMBRYOLOGY. 


sometimes  be  seen  apparently  extruding  globular  elements  which  simulate  the 
plates  in  appearance  and  staining  reaction.  3.  The  view  that  the  plates  are 
independent  nucleated  bodies  has  received  support  from  the  fact  that  they 
possess  faint  chromatic  masses  after  treatment  with  certain  dyes,  and  that  they 
possess  the  power  of  amoeboid  movement.  4.  The  recent  view  (Wright)  that 
"  the  blood  plates  are  detached  portions  of  the  cytoplasm  of  those  giant  cells  of 
the  bone  marrow  and  spleen,  which  have  been  named  megakaryocytes  by 
Howell"  is  strongly  supported  by  direct  observation. 

THE  LYMPHATIC  SYSTEM. 

The  Lymphatic  Vessels. 

From  a  genetic  standpoint  the  lymphatics  can  be  spoken  of  as  those  derived 
directly  from  veins  and  those  formed  from  intercellular  spaces  in  the  mesen- 
chyme.  The  lymphatics  derived  d  rectly  from  veins  are  confined  to  clearly 


Ant.  cardinal  vein   "~\       ' 


Right 

lymphatic  duct 
Subclavian  vein 


Post,  cardinal  vein" 

t 

Mesonephros' 

Kidney 

Sciatic  vein' 
Femoral  vein 


"{--  Ant.  lymph  heart 


Thoracic  duct 


"  Post,  lymph  heart 


FiG.  252. — Diagram  showing  the  arrangement  of  the  lymphatic  vessels 
in  a  pig  embryo  of  20  mm.     Sabin. 

circumscribed  regions  of  the  body,  namely,  the  region  of  certain  tributaries  of 
the  precardinal  and  postcardinal  veins  on  each  side,  and  are  spoken  of  as  the 
lymph  sacs  or  lymph  hearts.  The  lymphatics  formed  from  intercullar  spaces 
are  distributed  generally  throughout  the  body  and  represent  not  only  the  larger 
lymphatic  trunks,  apart  from  the  sacs  or  hearts  mentioned  above,  but  also 
all  the  finer  ramifications.  These  independently  formed  lymphatic  vessels 
are  spoken  of  as  systemic  lymphatics  in  contradistinction  to  the  sacs  or  hearts 
which  are  of  venous  origin. 


THE  DEVELOPMENT  OF  THE  VASCULAR  SYSTEM. 


277 


Two  pairs  of  lymph  sacs  develop,  the  jugular  lymph  sacs  in  the  cervical  and 
upper  thoracic  regions  in  relation  to  the  precardinal  veins  and  the  caudal  lymph 
sacs  in  the  lumbar  region  in  relation  to  the  postcardinal  veins.  Comparatively 
little  is  known  about  these  structures  in  the  human  embryo,  but  the  develop- 
rn^nt  of  the  jugular  lymph  sacs  in  the  domestic  cat  has  been  worked  out  with 
great  care  and  thoroughness  by  Huntington  and  McClure. 

As  stated  by  these  authors,  "the 
primary  principles  underlying  the  de- 
velopment of  the  jugular  lymph  sac  are: 
(i)  the  development  of  a  secondary 
channel  parallel  to  the  embryonic  pre- 
cardinal vein  and  the  Cuvierian  end  of 
the  post  cardinal;  (2)  the  association 
with  this  secondary  channel  of  a  certain 
number  of  dorsal  precardinal  tributaries, 
and  (3)  the  separation  of  these  two  sets 
of  venous  elements,  which  have  been 
termed  veno-lymphatics,  from  the  main 
venous  channels,  and  their  subsequent 
conversion  into  the  definite  jugular  lymph 
sacs  by  a  process  of  growth  and  fusion." 
A  number  of  venous  channels  along  the 
dorsal  side  of  the  straight  segment  of 
the  precardinal  and  the  cephalic  end  of 
the  postcardinal  vein  enlarge  and  begin 
to  coalesce.  The  first  four  dorsal  somatic 
tributaries  of  the  straight  segment  of  the 
precardinal  become  dilated  and  fuse 
together.  These  two  groups  of  venous 
channels  become  incorporated  into  a 
single  group  and,  by  a  further  process 
of  coalescence  of  their  component  ele- 
ments, form  a  sac-like  structure.  This  then  evacuates  its  blood  contents  into 
the  large  veins  and  becomes  completely  separated  from  the  venous  system. 
Subsequently  it  establishes  new  and  permanent  communication  with  the  venous 
system  either  in  the  angle  between  the  external  and  internal  jugular  veins — 
common  jugular  tap,  or  between  the  subclavian  and  common  jugular — jugulo- 
subclavian  tap,  or  at  both  points. 

The  systemic  lymphatic  trunks  join  the  lymph  sacs  and  through  them  open 
into  the  veins  at  the  points  mentioned  above,  the  sacs  thus  serving  as  portals 
of  entry  for  the  main  systemic  lymphatics  into  the  venous  system.  The  sacs 


FIG.  253. — Diagram  showing  network  of 
lymphatic  vessels  in  skin  of  pig  embryos. 
Sabin. 

Area  marked  A  shows  extent  of  network  in 
an  embryo  of  18  mm.;  B,  in  embryo  of 
20  mm.;  C,  in  embryo  of  30  mm.;  D,  in 
embryo  of  40  mm. 


278 


TEXT-BOOK  OF  EMBRYOLOGY. 


become  relatively  reduced  in  size  during  later  development,  although  in  the 
adult  there  is  fairly  well  marked  dilatation. 

The  first  studies  by  Sabin  on  the  developing  lymph  sacs  or  hearts  in  the 
pig  led  to  the  conclusion  that  they  were  outgrowths  from  the  large  veins.  Sub- 
sequent reasearches  on  the  rabbit  by  Lewis,  who  was  the  first  investigator  to 
furnish  the  clue  for  the  proper  interpretation  of  the  mammalian  jugular  lymph 
sacs,  and  by  Huntington  and  McClure  on  the  cat,  have  resulted  in  practical 


Ant.  cardinal  vein 
Subclavian  vein 

Post,  cardinal  vein   — /-/ — 


Diaphragm- 


Suprarenal  gland 
Mesonephros 

Kidney—- 


Ant, lymph  heart 

Deep  lymphatics 

of  arm 


Branches  to  heart 

Branches  to  lung 

Aorta 

Branch  to  oesophagus 
•'Branches  to  stomach 
"Branch  to  duodenum 

~~~r  Branches  to  mesenteric  plexus 
•    Cisterna  chyli 


Post,  lymph  heart 

""••j  Deep  lymphatics . 
to  leg 

FIG.  254. — Diagram  showing  the  arrangement  of  the  lymphatic  vessels  in  a 
pig  embryo  of  40  mm.     Sabin. 

unanimity  of  opinion  that  the  structures  in  question  are  derived  directly  from 
veins,  but  are  not  outgrowths  from  the  large  venous  trunks. 

So  far  as  the  development  of  the  lymph  sacs  or  hearts  in  other  vertebrate 
forms  is  concerned,  the  excellent  work  of  Sala  on  the  caudal  lymph  hearts  in  the 
chick,  the  observations  of  Mierzejewski  and  others  on  the  jugular  lymph  sacs 
in  the  chick,  and  the  careful  and  thorough  investigations  of  Huntington  on  the 
caudal  and  jugular  lymph  sacs  in  reptilian  forms,  all  illustrate  the  general 
principle  that  the  lymph  sacs  or  hearts  are  direct  venous  derivatives  and  that 
there  is  a  decided  uniformity  in  the  manner  of  development  of  these  homol- 
ogous structures  In  the  different  vertebrate  classes. 


THE  DEVELOPMENT  OF  THE  VASCULAR  SYSTEM.  279 

In  regard  to  the  origin  and  development  of  the  mammalian  systemic  lymph- 
atics, some  of  the  earlier  investigators  held  that  they  were  outgrowths  from 
preexisting  vascular  channels.  Sabin  maintained  that  the  lymph  hearts  were 
centers  from  which  the  rest  of  the  lymphatics  developed  by  evagination  or 
outgrowth  (Figs.  252,  253  and  254).  Lewis  claimed  that  the  lymphatic  vessels 
grew  out  not  only  from  the  lymph  hearts  but  also  from  the  veins  at  many 


.Cellular  mass 


,  Mesenchyme 


:'--.'•••-  "-.- .-    "^  Marginal  plexus 


FlG.  255. — From  a  section  through  the  axilla  of  a  human  embryo  of  106  mm. 
(about  4  months),  showing  anlagen  of  lymph  glands.     Kling. 

points.  Subsequent  researches  of  Huntlngton  and  McClure  and  of  Huntington 
himself  have  furnished  conclusive  evidence,  so  far  as  such  evidence  can  be  ob- 
tained from  sections  of  embryos,  that  the  systemic  lymphatics,  not  only  the 
larger  trunks  but  also  the  smaller  ramifications,  arise  independently  of  the 
haemal  vascular  system  by  confluence  of  mesenchymal  intercellular  spaces  and 
become  lined  by  lymphatic  vascular  endothelium  which  represents  modified 
mesenchymal  cells  lining  those  spaces. 

The  Lymph  Glands. 

The  lymph  glands  do  not  begin  to  develop  for  some  t'.me  after  the  lymphatic 
vessels,  since  there  are  no  indications  of  them  in  the  human  foetus  until  the  latter 
part  of  the  third  month  and  none  in  pig  embryos  until  they  have  reached  a 
length  of  30  mm.  While  it  is  definitely  settled  that  lymph  glands  originate 
in  very  close  relation  with  the  lymphatic  vessels,  certain  points  in  their  latter 
development  need  further  study.  In  the  axilla  and  groin,  for  example,  the 
lymphatic  vessels  form  a  dense  network  in  the  meshes  of  which  are  masses  of 
connective  tissue.  These  masses  become  more  cellular  and  with  the  surround- 


280  TEXT-BOOK  OF  EMBRYOLOGY. 

ing  vessels  constitute  the  anlagen  of  lymph  glands  (Fig.  255).  The  new  cells 
which  appear  in  the  masses  are  lymphocytes  which  may  pass  through  the  walls 
of  the  neighboring  blood  vessels  and  lodge  here  or  may  be  derived  directly  from 
connective  tissue  (mesenchymal)  cells  in  situ.  Whatever  the  origin  of  the 
lymphocytes  may  be,  they  have  the  opportunity  here  to  divide  freely.  The 
mass  becomes  still  more  cellular  and  enlarges  at  the  expense  of  the  lymphatic 
vessels  which  then  come  to  form  a  network  around  the  mass.  This  network  is 
the  marginal  plexus,  and  it  communicates  freely  with  the  neighboring  lymph- 
atic channels.  Within  the  mass  of  cells  blood  vessels  are  present  from  the  begin- 
ning, and  these  are  destined  to  be  the  blood  vessels  of  the  lymph  gland,  and  the 
point  of  their  entrance  and  exit  marks  the  hilus.  Outside  of  the  marginal 

Efferent  lymph,  ves. 


•',  '     -t  ' -1-  -,'•';  \-  '  "V/  yV        Bloodvessel 

'.''',/  '&'~'^&S*Jr?) 


/'V**?'?  "'  * '  '''i.j^^Marginal  sinus 

^' ' -«^-' 'i1'^'  "'••'"••  '••'    .••'•.' 

•*,    £;'./  •   '•'    "^A Capsule 

V.  '* 


^M1 


Afferent       „..,.. ^..';..V  '"~-  ,': 
lymph,  ves.        \  ^,    l(  .J,1  '  / 
t,.    -"'.i 

FIG.  256. — From  a  section  through  the  axilla  of  a  human  embryo  of  125  mm.  (4-5  months), 
showing  an  early  stage  of  a  lymph  gland.     Kling. 

plexus  the  connective  tissue  condenses  to  form  the  capsule.  The  gland  at  this 
stage  thus  consists  of  a  central  compact  cellular  mass,  made  up  of  connective 
tissue  and  lymphocytes,  in  which  blood  vessels  ramify;  a  plexus  of  lymphatic 
channels  around  the  mass  which  communicate  with  the  neighboring  channels; 
and  around  the  whole  structure  a  capsule  of  connective  tissue  (Fig.  256). 

Further  development  consists  of  the  breaking  up  of  the  cell  mass  by  lymph- 
atic channels  and  the  formation  of  the  follicles.  It  seems  probable  that 
branches  from  the  marginal  plexus  invade  the  cell  mass  principally  from  an 
area  around  the  hilus,  thus  breaking  it  up  into  smaller  irregular  masses  or  cords. 
At  the  side  opposite  the  hilus  the  invading  channels  are  less  numerous,  leaving 
larger  parts  of  the  mass  which  become  the  follicles  (nodules)  of  the  cortex.  On 
all  sides  the  invading  channels  communicate  with  the  marginal  plexus  and  form 
the  so-called  intermediary  plexus.  The  gland  as  a  whole  enlarges  and  its  per- 


THE   DEVELOPMENT  OF  THE   VASCULAR   SYSTEM. 


281 


ipheral  part  pushes  outward  into  the  surrounding  tissue.  Over  the  follicles  the 
capsule  is  pushed  outward,  while  between  them  it  remains  in  place  and  comes  to 
dip  into  the  gland  as  the  trabecultz.  The  blood  vessels  tend  to  lie  in  the 
trabeculae,  but  a  small  branch  probably  passes  to  each  follicle.  In  the  follicles 
themselves  the  lymphocytes  proliferate  and  the  central  part  of  each  follicle 
becomes  a  germinal  center.  The  connective  tissue  among  the  lymphatic  vessels 
composing  the  marginal  plexus  becomes  proportionately  less  as  the  vessels 
enlarge  and  finally  exists  only  as  strands  of  reticular  tissue  which,  naturally,  are 
covered  by  the  endothelium;  thus  the  marginal  plexus  becomes  the  marginal 
sinus.  The  intermediary  sinus  is  formed  by  the  channels  which  originally  in- 
vaded the  cell  mass.  The  reticular  tissue  is  probably  composed  of  remnants 


Afferent  lymphatic  vessels 


Marginal  sinus 


—Marginal  sinus  (plexus) 
Capsule 
Trabecula 
.Reticular  tissue 


Intermediary 
plexus 


Efferent  lymph,  vessel  Blood  vessels 


FIG.  257. — Diagram  illustrating  a  stage  (later  than  Fig.  256)  in  the  development 
of  a  lymph  gland.     Stohr. 

of  the  original  connective  tissue.  All  the  channels  converge  at  the  hilus  to 
form  the  efferent  lymphatic  vessels  (Figs.  257  and  258). 

The  haemolymph  glands  are  probably  developed  in  much  the  same  manner 
as  the  lymph  glands  except  that  in  the  former  the  sinuses  are  composed  of  blood 
vessels  instead  of  lymphatic  vessels. 

The  first  lymph  glands  to  develop  are  those  in  the  axilla,  in  the  inguinal 
region,  in  the  neck,  and  in  the  base  of  the  mesentery.  These  are  the  so-called 
primary  glands  and  develop  during  foetal  life.  They  are  of  constant  occur- 
rence in  these  regions,  but  vary  in  number  in  different  individuals.  The 
secondary  lymph  glands  are  those  in  the  bend  of  the  elbow,  in  the  popliteal  space, 
in  the  mesentery,  and  around  the  aorta.  Some  of  these  develop  during 


282 


TEXT-BOOK  OF  EMBRYOLOGY. 


foetal  life  and  some  later.  While  lymph  glands  are  of  constant  occurrence  in 
some  regions  throughout  life,  the  number  may  vary  at  different  times  in  any 
region;  and  there  may  also  be  variations  in  different  individuals.  Glands  may 
be  called  into  existence  at  any  time  during  life,  in  almost  any  region,  as  the 
result  of  exceptional  activity  of  some  organ,  or  in  pathological  conditions. 
Such  structures  are  known  as  tertiary  lymph  glands. 

The  origin  of  the  lymph  (plasma)  itself  is  probably  extremely  complex.     At 
one  time  it  was  considered  as  the  result  of  filtration  from  the  blood  plasma 


Afferent  lymph,  vessels 


Lymph  follicle 


Marginal 
plexus 


Intermediary, 
plexus 


Trabecula 


Capsule  rtf^~~ 

Efferent  lymph,  vessels 

FIG.  258. — Diagram  illustrating  a  late  stage  in  the  development  of  a  lymph  gland. 
Compare  with  Fig.  257.     Stohr. 

through  the  capillary  walls.  If  lymph  originates  in  this  way  the  filtration  is 
selective,  for  the  chemical  composition  of  the  lymph  differs  from  that  of  the 
blood  plasma.  Further  researches  have  tended  to  indicate  that  the  lymph 
plasma  may  be  the  product  of  the  vital  activities  of  cells. 

The  Spleen. 

Since  the  spleen  is  generally  considered  as  a  lymphatic  organ  and  since  re- 
cent researches  have  shown  that  its  structure  is  quite  comparable  to  that  of  the 
lymph  glands,  it  seems  advisable  to  consider  it  under  the  head  of  lymphatic 
organs.  Its  ultimate  origin  is  not  yet  settled  and  the  details  of  its  later  develop- 
ment are  still  obscure.  The  same  difficulties  are  met  with  as  in  the  case  of 
the  origin  and  development  of  blood  cells,  for  it  is  known  that  the  spleen  plays 
a  part  in  the  formation  of  the  blood  cells.  Its  structure  differs  from  that  of  the 
lymph  glands  chiefly  in  that  it  possesses  no  distinct  lymphatic  sinuses;  but  it  does 
possess  lymph  follicles  (splenic  corpuscles)  and  densely  cellular  cords  (pulp  cords) 
which  are  separated  by  cavernous  blood  vessels  (cavernous  veins) . 


THE   DEVELOPMENT  OF  THE   VASCULAR   SYSTEM. 


283 


For  some  time  the  spleen  was  considered  as  a  derivative  primarily  of  the 
mesenchyme  in  the  region  of  the  dorsal  mesogastrium.  More  recently,  how- 
ever, investigators  have  taken  the  view  that  it  arises  partly,  or  possibly  entirely, 
from  the  mesothelium  (ccelomic  epithelium)  of  the  dorsal  mesogastrium.  In 
human  embryos  during  the  fifth  week  the  anlage  of  the  spleen  appears  as  an 
elevation  on  the  left  (dorsal)  side  of  the  mesogastrium  (Fig.  259).  This  eleva- 
tion is  produced  by  a  local  thickening  and  vascularization  of  the  mesenchyme, 


Aorta 


Omental 
bursa 


Right  side 


Mesonephros 


Spleen 


Dorsal 

mesogastrium 
(greater  omentum) 


Abdominal  cavity 
(coslom) 


Stomach 
Left  side 


Bile  duct        Ventral  mesogastrium 
(lesser  omentum) 

FIG.  259. — From  transverse  section  through  stomach  region  of  a  14  mm. 
pig  embryo.     Photograph. 


accompanied  by  a  thickening  of  the  mesothelium  which  covers  it;  and,  further- 
more, the  mesothelium  is  not  so  distinctly  marked  off  from  the  mesenchyme  as 
in  other  regions.  Cells  from  the  mesothelium  then  migrate  into  the  subjacent 
mesenchyme  and  the  latter  becomes  much  more  cellular  (Fig.  260).  The 
migration  is  brief,  and  in  embryos  of  about  forty-two  days  has  ceased,  and  the 
mesothelium  is  again  reduced  to  a  single  layer  of  cells.  The  elevation  becomes 
larger  and  projects  into  the  body  cavity.  At  first  it  is  attached  to  the  mesentery 
(mesogastrium)  by  a  broad,  thick  base,  but  as  development  proceeds  the  at- 


284 


TEXT-BOOK  OF  EMBRYOLOGY. 


tachment  becomes  relatively  smaller  and  finally  forms  only  a  narrow  band  of 
tissue  through  which  the  blood  vessels  (splenic  artery  and  vein)  pass. 

Further  development  of  the  substance  of  the  spleen  consists  of  the  breaking 
up  of  the  cellular  mesenchymal  tissue  by  blood  vessels  and  the  formation  of  the 
splenic  corpuscles.  The  connective  tissue  trabecula,  as  well  as  the  capsule  of 
the  spleen  are  derived  from  the  original  mesenchymal  tissue.  The  blood 
vessels  become  dilated  in  parts  of  their  course  to  form  the  cavernous  vessels 
(cavernous  veins')  which  are  separated  by  the  pulp  cords.  The  connective 
(reticular)  tissue  of  the  pulp  cords  is  a  derivative  of  the  mesenchyme,  but  the 
origin  of  the  various  types  of  cells  in  the  cords  is  not  certain.  The  adventitia  of 


Mesothelium        Anlage  of  spleen 
\ 


Mesenchyme 


Migrating  cells  s 


"   ..  "       "©-        £  $ 


FIG.  260. — From  section  through  dorsal  mesogastrium  (anlage  of-spleen)  of  a  chick  embryo 
of  3  days  and  21  hours  incubation.    Tonkoff. 

tne  walls  of  some  of  the  small  arteries  becomes  infiltrated  with  lymphocytes  to 
form  the  splenic  corpuscles  (lymph  follicles). 

It  is  not  at  all  improbable  that  during  foetal  life  the  spleen  is  a  hemato- 
poietic  organ,  that  is,  both  leucocytes  and  nucleated  red  blood  cells  proliferate 
within  it.  Normally,  the  formation  of  erythrocytes  stops  at  or  soon  after 
birth.  In  severe  anaemia  or  in  pernicious  anaemia  in  postnatal  life,  however, 
the  presence  of  dividing  nucleated  red  blood  cells  suggests  a  return  to 
embryonic  conditions.  Still  the  question  arises  as  to  the  origin  of  these  nucle- 
ated forms  (ery throblasts) .  It  has  also  been  suggested  that  the  spleen  acts  as  a 
destroyer  of  worn-out  erythrocytes,  for  in  many  cases  apparent  remnants  of 
the  latter  have  been  observed  within  the  cytoplasm  of  the  "spleen  cells."  The 
lymphocytes  proliferate  to  a  certain  extent  in  the  splenic  corpuscles,  and  in  that 
way,  at  least,  the  spleen  serves  as  a  base  of  supply  for  leucocytes.  There  is  a 


THE   DEVELOPMENT   OF  THE  VASCULAR  SYSTEM.  285 

possible  suggestion  that  the  first  leucocytes  of  the  spleen  have  their  origin  in  the 
mesenchymal  cells  of  the  spleen  anlage.  This  would  be  in  accord  with  the 
observations  which  indicate  that  leucocytes  are  derived  from  indifferent 
mesenchyme  cells. 

Glomus  Coccygeum. 

The  coccygeal  skein  (coccygeal  gland)  was  originally  considered  as  belong- 
ing to  the  same  category  as  the  suprarenal  glands,  but  the  latest  researches  have 
indicated  that  its  cells  do  not  possess  the  characteristic  chromafnn  reaction  and 
that  it  belongs  rather  to  the  category  of  lymph  glands.  It  develops  ventral 
to  the  apex  of  the  coccyx  in  relation  with  branches  of  the  middle  sacral  artery. 

Although  the  thymus  gland  becomes  a  lymphatic  structure  it  is  primarily 
derived  from  the  epithelium  (entoderm)  of  the  branchial  grooves  and  will  be  con- 
sidered in  connection  with  the  development  of  the  alimentary  tract  (Chap.  XII). 
The  tonsils  also  will  be  considered  in  the  same  connection. 

Anomalies. 

ANOMALIES  or  THE  HEART. 

ACARDIA. — The  malformation  known  as  acardia  occurs  in  the  case  of  twins 
that  have  but  one  chorion.  The  so-called  acardiac  condition  does  not  neces- 
sarily imply  the  absence  of  the  heart  in  the  affected  twin,  for  the  latter  may 
develop  to  a  considerable  degree  and  possess  a  functionating  heart.  On  the 
other  hand,  the  affected  twin  may  be  only  an  amorphous  mass  of  tissue  which 
derives  its  total  blood  supply  through  the  agency  of  the  stronger  twin's  heart. 
Or  there  may  be  any  intermediate  form  between  these  two  extremes.  The 
point  is  that  the  acardiac  monster  (acardiacus)  derives  its  blood  wholly  or  in 
part  through  the  agency  of  the  stronger  heart.  A  further  discussion  of  acardiac 
monsters  and  their  possible  explanation  will  be  found  in  Chap.  XIX. 

DOUBLE  HEART. — But  one  or  two  cases  of  a  double  heart  in  a  single  human 
foetus  have  been  recorded.  In  some  of  the  lower  forms  (chick)  it  occurs  more 
frequently.  The  explanation  is  probably  to  be  found  in  the  double  origin  of 
the  heart  in  Amniotes  (p.  222). 

ANOMALOUS  POSITION  OF  THE  HEART. — Congenital  anomalies  in  the  posi- 
tion of  the  heart  are  rare.  Dextrocardia  (heart  on  the  right  side)  is  almost 
invariably  associated  with  changes  in  the  position  of  the  viscera  (see  transposi- 
tion of  the  viscera,  page  355).  In  the  condition  known  as  ectopia  cordis,  the 
heart,  with  the  pericardium,  protrudes  through  a  cleft  in  the  ventral  wall  of 
the  thorax,  the  cleft  being  probably  due  to  an  imperfect  fusion  of  the  two  sides 
of  the  body  wall  in  that  particular  region. 

ANOMALIES  OF  THE  SEPTA. — The  most  frequent  anomaly  in  the  atrial 


286  TEXT-BOOK  OF  EMBRYOLOGY. 

septum  is  the  persistence  of  the  foramen  ovale.  The  entire  foramen  may 
remain  patent,  or,  as  is  more  frequently  the  case,  a  smaller  opening  may  per- 
sist between  the  ventral  (anterior)  border  of  the  foramen  and  the  valve  of  the 
latter  (p.  229). 

The  atrial  septum  may  be  wholly  lacking,  but  this  always  occurs  in  conjunc- 
tion with  other  defects.  It  sometimes  happens  that  the  primary  atrial  septum 
(septum  superius),  which  grows  from  the  cephalic  side  of  the  common  chamber, 
fails  to  fuse  with  the  septum  of  the  atrio-ventricular  aperture  (p.  229  and 
Fig.  200). 

Defects  in  the  ventricular  septum  occur  less  frequently  than  in  the  atrial 
septum.  It  may  happen  that  the  cephalic  (upper)  border  of  the  ventricular 
septum  fails  to  fuse  with  the  septum  which  divides  the  aortic  trunk  and  bulb 
into  the  aorta  and  pulmonary  artery.  This  affects  the  cephalic  (upper)  part  of 
the  septum  sometimes  called  the  pars  membranacea  (p.  230  and  Fig.  203) ;  and 
since  the  defect  is  situated  near  the  opening  of  the  aorta  it  brings  about  the  so- 
called  "origin  of  the  aorta  from  both  ventricles."  Stenosis  of  the  pulmonary 
artery  usually  accompanies  this  condition.  Rarely  is  there  a  deficiency  in  the 
caudal  (lower)  part  of  the  ventricular  septum.  Complete  absence  of  the 
ventricular  septum  may  occur,  and  along  with  it  also  an  absence  of  the  atrial 
septum,  so  that  the  heart  is  simply  two-chambered;  or  the  single  ventricle  may 
open  into  two  atria.  The  causes  of  these  defects  are  obscure. 

ANOMALIES  OF  THE  VALVES. — There  may  be  congenital  variations  in  the 
size  and  number  of  the  atrio-ventricular  valves,  depending  upon  abnormal  posi- 
tion,  fusion,  or  division  of  the  pad-like  masses  from  which  the  valves  develop 
(p.  232). 

There  may  be  also  a  greater  or  lesser  number  of  semilunar  valves  in  the 
aorta  and  pulmonary  artery.  This  irregularity  can  probably  be  referred  back  to 
an  atypical  division  of  the  aortic  trunk  and  bulb,  and  a  corresponding  atypical 
division  of  the  protuberances  which  give  rise  to  the  valves  (p.  232).  Variations 
in  the  valves  may  or  may  not  be  accompanied  by  functional  disturbances. 
The  congenital  diminution  in  the  number  of  valves  should  be  distinguished 
from  the  acquired,  where  chronic  endocarditis  may  cause  a  fusion. 

ANOMALIES  OF  THE  LARGE  VASCULAR  TRUNKS. 

ANOMALIES  OF  THE  ARTERIES. — There  may  be  a  transposition  of  the  aorta 
and  pulmonary  artery.  This  results  from  an  anomalous  division  of  the  aortic 
trunk  and  bulb.  The  partition  develops  in  such  a  way  as  to  put  the  aorta  in 
communication  with  the  right  ventricle,  and  the  pulmonary  artery  with  the  left 
ventricle  (p.  230).  Or  the  aorta  and  pulmonary  artery  may  remain  in  direct 
communication  on  account  of  an  imperfect  development  of  the  partition. 
Rarely  the  two  vessels  remain  as  a  common  stem. 


THE   DEVELOPMENT  OF  THE   VASCULAR   SYSTEM.  287 

Congenital  stenosis  (constriction)  of  the  pulmonary  artery  may  occur,  ac- 
companied by  an  increase  in  the  size  of  the  aorta,  possibly  due  to  an  unequal 
division  of  the  aortic  trunk  and  bulb.  After  birth  little  or  no  blood  can  pass  to 
the  lungs,  and  the  result  is  a  general  damming  (stasis)  of  the  venous  blood  with 
marked  cyanosis.  This  is  at  least  one  explanation  of  the  so-called  "blue 
babies."  Less  frequently  there  is  a  stenosis  of  the  proximal  end  of  the  aorta, 
with  excessive  size  of  the  pulmonary  artery,  also  due  to  an  unequal  division  of 
the  aortic  trunk  and  bulb  (p.  230).  These  stenoses  are  usually,  though  not 
always,  accompanied  by  defects  in  the  ventricular  septum. 

Persistence  of  the  ductus  arteriosus  may  occur  without  any  other  defect;  but 
usually  the  persistence  is  associated  with  anomalous  conditions  of  the  aorta  and 
pulmonary  artery. 

Occasionally  the  arch  of  the  aorta  is  found  on  the  right  side.  This  condition 
is  due  to  the  persistence  of  the  fourth  aortic  arch  on  the  right  side  instead  of  the 
corresponding  arch  on  the  left  side;  this  is  the  normal  condition  in  Birds. 
Rarely  both  fourth  aortic  arches  persist,  which  results  in  a  double  arch  of  the 
aorta — the  normal  condition  in  Reptiles.  (Compare  Figs.  219  and  220.) 

The  dorsal  aorta,  particularly  the  abdominal  part,  is  occasionally  found  to 
consist  of  two  parallel,  imperfectly  separated  vessels — a  condition  known  as 
double  aorta.  This  anomaly  is  due  to  an  imperfect  fusion  of  the  two  primitive 
aortae  (p.  239  and  Fig.  194). 

Numerous  variations  are  met  with  in  the  larger  branches  of  the  aorta,  many 
of  which  are  explained  by  referring  them  to  embryonic  conditions.  Especially 
noteworthy  are  the  branches  from  the  arch  of  the  aorta,  since  their  development 
is  so  closely  associated  with  the  changes  in  the  aortic  arches.  The  normal 
arrangement,  passing  from  the  heart,  is  innominate  artery,  left  common 
carotid  artery,  left  subclavian  artery  (see  Fig.  220). 

1.  All  these  branches  may  be  collected  into  a  single  trunk,  a  condition 
characteristic  of  the  horse. 

2.  Two  branches  may  arise  from  the  arch,     (a)  The  left  common  carotid 
unites  with  the  innominate,  and  the  left  subclavian  arises  separately.     This  is 
the  normal  arrangement  among  the  apes,  and  is  probably  the  most  common 
variation  in  man.     (b)  Very  rarely  there  are  two  innominate  arteries,  each 
formed  by  the  union  of  a  common  carotid  and  subclavian — a  condition  char- 
acteristic of  Birds. 

3.  Three  branches  may  arise  from  the  arch  but  in  a  manner  differing  from 
the  normal.    Each  subclavian  arises  separately  and  the  two  common  carotids 
are  united  into  a  single  vessel.     This  arrangement  is  found  in  some  of  the 
Cetacea. 

4.  Four  vessels  may  arise  from  the  arch,     (a)  These  are,  in  order,  innomi- 
nate, left  common  carotid,  left  vertebral,  left  subclavian.   (b)  Or  the  order  may 

19 


288  TEXT-BOOK  OF  EMBRYOLOGY. 

be  right  common  carotid,  left  common  carotid,  left  subclavian,  right  subclavian. 
In  this  case  the  proximal  part  of  the  right  subclavian  represents  the  portion  of 
the  right  dorsal  aortic  root  just  cranial  to  the  bifurcation;  the  fourth  arch  on 
the  right  side  disappears,  (c)  Or  very  rarely  the  order  may  be  right  subclavian, 
right  common  carotid,  left  common  carotid,  left  subclavian. 

5.  Five  branches  of  the  arch  are  rare.     In  order  they  are  right  subclavian, 
right  vertebral,  right  common  carotid,  left  common  carotid,  left  subclavian. 

6.  Very  rarely  there  are  six  branches  of  the  arch;   right  subclavian,  right 
vertebral,  right    common    carotid,  left   common  carotid,  left  vertebral,  left 
subclavian. 

ANOMALIES  OF  THE  VEINS. — The  two  pulmonary  veins  on  each  side,  more 
frequently  those  on  the  left  side,  may  unite  into  a  common  trunk  before  opening 
into  the  atrium.  This  variation  is  probably  due  to  the  fact  that  the  absorption 
of  the  originally  single  pulmonary  trunk  into  the  wall  of  the  atrium  does  not 
proceed  far  enough  to  cause  all  four  of  the  pulmonary  veins  to  open  separately 
(see  p.  231).  The  upper  (more  cephalic)  vein  on  the  right  side  may  open  into 
the  superior  vena  cava;  or  the  upper  vein  on  the  left  side  may  open  into  the  left 
innominate  vein.  A  possible  explanation  for  this  is  that  the  pulmonary  veins 
are  formed  after  the  heart  and  other  vessels  have  developed  to  a  considerable 
degree,  and  some  of  them  may  unite  with  the  other  vessels  instead  of  with  the 
atrium. 

Occasionally  two  superior  vena  cava  are  met  with.  In  this  case  the  right 
opens  into  the  right  atrium  in  the  normal  position;  the  left  opens  into  the  right 
atrium  through  the  coronary  sinus  which  naturally  is  much  enlarged.  This 
condition  represents  a  persistence  of  the  proximal  end  of  the  left  anterior  car- 
dinal vein  and  the  left  duct  of  Cuvier,  and  is  the  normal  arrangement  in  many 
of  the  lower  Vertebrates.  Even  with  two  venae  cavae  there  may  be  a  small  anas- 
tomosing branch  in  the  position  of  the  left  innominate  vein,  which  represents 
the  normal  structure  in  the  Marsupials  (see  Figs.  232  and  233  and  p.  256). 
There  are  a  few  cases  on  record  of  a  single  left  superior  vena  cava. 

The  inferior  vena  cava  is  also  subject  to  variations  which  represent  the 
abnormal  persistence  of  certain  embryonic  vessels.  Perhaps  the  most  striking 
of  these  variations  is  the  condition  known  as  double  inferior  vena  cava.  There 
may  be  two  parallel  vessels,  of  equal  or  unequal  size,  which  unite  at  or  above 
the  level  of  the  renal  veins.  This  condition  is  to  be  explained  by  the  persistence 
of  parts  of  both  posterior  cardinal  veins.  It  is  met  with  not  infrequently  among 
the  lower  Mammals,  especially  the  Marsupials  (see  Figs.  233  and  236). 

Rarely  the  inferior  vena  cava  opens  into  the  superior,  and  in  this  case  thf 
hepatic  veins  open  directly  into  the  right  atrium.  This  anomaly  probablj 
represents  a  failure  of  the  absorption  of  the  sinus  venosus  into  the  wall  of  th( 
atrium  (p.  231). 


THE  DEVELOPMENT   OF  THE  VASCULAR   SYSTEM.  289 

A  left  renal  vein  may  open  into  the  left  common  iliac,  which  condition 
represents  a  persistence  of  the  more  caudal  part  of  the  left  posterior  cardinal 
(Fig.  236).  This  anomaly  is  rare. 

The  azygos  vein  occasionally  presents  variations  which  are  due  to  anoma- 
lous development.  All  the  intercostal  veins  on  the  left  side  may  be  collected 
into  a  vessel  which  opens  into  the  left  innominate  vein.  There  may  be  a  single 
median  azygos  vein;  or  there  may  be  a  transposition  of  the  azygos  vein.  It  may 
be  on  the  left  side  and  open  into  the  coronary  sinus  (normal  conditions  in  the 
sheep  and  a  few  other  Mammals) .  The  latter  condition  represents  a  persistence 
of  the  more  cephalic  part  of  the  left  posterior  cardinal  vein  (see  Figs.  233  and  234) . 

Space  does  not  permit  a  discussion  of  the  great  number  of  congenital  varia- 
tions that  occur  in  the  smaller  blood  vessels,  both  arteries  and  veins.  The 
student  is  referred,  however,  to  the  more  extensive  text-books  of  anatomy. 

PRACTICAL  SUGGESTIONS. 

The  development  of  the  vascular  system  (blood  vessels,  lymphatic  vessels  and  blood) 
presents  some  of  the  greatest  difficulties  of  study  in  embryology.  The  development  of  the 
blood  cells  and  the  formation  of  the  primary  blood  vessels  may  be  studied  by  means  of 
ordinary  histological  technic.  But  in  order  to  trace  the  development  of  such  complicated 
systems  as  the  blood  vessels  and  lymphatic  vessels,  other  methods,  in  addition  to  ordinary 
histological  technic,  must  be  employed;  for  it  is  obvious  that  a  few  sections  taken  at  random 
in  an  embryo  would  be  practically  valueless  in  tracing  the  course  of  a  vessel.  These  addi- 
tional methods,  as  referred  to  in  the  following  paragraphs,  will  be  described  in  the  Appendix. 

The  Blood. — The  blood  islands  are  very  well  shown  in  surface  views  of  the  chick  blasto- 
derm. The  most  instructive  specimens  are  obtained  during  the  latter  part  of  the  first  and 
during  the  second  day  of  incubation.  The  blastoderm  is  removed  from  the  egg,  fixed  in 
Zenker's  fluid,  stained  in  toto  with  borax-carmin  and  mounted  in  toto  in  xylol-damar. 

To  complete  the  study,  sections  of  blastoderms  of  similar  stages  are  also  necessary.  In 
this  case  Flemming's  fluid  is  an  excellent  fixative  (Zenker's  is  good,  but  causes  more  shrink- 
age). Sections  are  cut  in  paraffin,  stained  with  Heidenhain's  hsematoxylin  and  mounted 
in  xylol-damar. 

In  later  stages  the  blood  cells  may  be  observed  in  the  vessels  in  sections  of  any  embryo  (see 
following  paragraphs).  The  best  region  is  the  liver,  where  the  cells  are  always  present  in 
great  numbers. 

Very  instructive  specimens  may  be  obtained  by  making  smears,  at  any  stage  during 
embryonic  life,  from  a  fresh  liver  or  spleen,  or  from  the  bone  marrow,  allowing  the  smear 
to  dry,  staining  with  Jenner's  blood  stain  and  mounting  in  xylol-damar.  In  such  specimens 
all  types  of  blood  cells  may  be  seen. 

The  Blood  Vessels. — Surface  view  of  the  chick  blastoderm  during  the  second  and  third 
(and  even  later)  days  of  incubation  show  the  developing  blood  vessels  in  the  extraembryonic 
area,  and  also  show  the  relation  between  the  vessels  and  blood  islands.  The  blastoderm 
is  removed  from  the  egg,  fixed  in  Zenker's  fluid,  stained  in  toto  with  borax-carmin  and 
mounted  in  toto  in  xylol-damar. 

Sections  of  the  blastoderm  at  such  stages  are  necessary  to  complete  the  picture  one  gets 
on  surface  view.  The  blastoderm  is  fixed  in  Flemming's  fluid  or  Zenker's  fluid,  sectioned 
in  paraffin,  stained  with  Heidenhain's  haematoxylin  and  mounted  in  xylol-damar.  The  for- 


290  TEXT-BOOK  OF  EMBRYOLOGY. 

mation  of  the  primitive  blood  vessels  is  seen  in  the  visceral  mesoderm.  The  vessels  often 
contain  masses  of  nucleated  cells  (erythroblasts)  derived  from  the  blood  islands 

The  study  of  the  developing  vessels  within  the  embryo  is  much  more  difficult,  requiring 
complete  serial  sets  of  sections  at  different  stages,  and  involving  tedious  methods  of  recon- 
struction. Any  particular  vessel  at  one  stage  must  be  traced  from  section  to  section  through- 
out its  entire  length,  and  its  relations  to  other  vessels  and  to  surrounding  structures  must  be 
observed.  Furthermore,  such  observations  must  be  made  at  many  different  stages.  It  is 
obviously  impossible  to  retain  a  clear  mental  picture  of  all  such  vessels  throughout  a  series 
of  observations;  consequently  it  is  necessary  to  reconstruct  graphically  or  otherwise  the 
vessels  in  the  succeeding  stages  in  order  to  make  comparisons  and  observe  the  progress  of 
development. 

For  the  successful  study  of  developing  blood  vessels  (and  lymphatic  vessels)  two  things 
are  essential: 

1.  In  the  first  place  the  embryo  at  any  particular  stage  must  be  treated  in  such  a  manner 
as  to  differentiate  the  vessels  from  the  surrounding  tissues,  and  so  enable  one  to  reestablish 
their  continuity  throughout  a  long  series  of  sections.     The  differentiation  of  the  vessels  is 
usually  obtained  by  the  use  of  certain  stains  which  have  strong  affinities  for  blood  cells. 
A  chick  embryo  or  mammalian  embryo  is  fixed  in  Zenker's  fluid.     As  much  blood  as  possi- 
ble should  be  left  in  the  vessels.     The  embryo  is  embedded  in  paraffin  and  cut  into  trans- 
verse serial  sections,  care  being  taken  to  have  the  series  complete.     The  technic  for  serial 
sections  will  be  found  in  the  Appendix. 

The  method  of  staining  is  as  follows: 

1.  Xylol,  graded  alcohols,  water. 

2.  Weigert's  haematoxylin,  several  minutes. 

3.  Rinse  in  water. 

4.  Decolorize  in  water  acidulated  with  HC1  (six  drops  to  50  c.c.  of  water)  until 
tissues  appear  gray. 

5.  Rinse  in  water. 

6.  Dip  in  water  containing  a  few  drops  of  ammonia  (three  drops  to  50  c.c.  of 
water)  until  tissues  are  blue. 

7.  Rinse  thoroughly  in  distilled  water. 

8.  One-half  to  i  per  cent,  solution  of  Orange  G.  in  distilled  water  until  tissues 
acquire  a  brownish  tinge. 

9.  Rinse  in  distilled  water. 

10.  Graded  alcohols,  xylol,  xylol-damar. 

This  method  gives  the  blood  cells  a  bright  orange  color,  thus  differentiating  the  vessels 
from  the  surrounding  tissues.  In  case  the  blood  does  not  take  the  stain  readily,  a  drop  of 
acid  (acetic  is  good)  in  the  Orange  G.  solution  (one  drop  to  100  c.c.)  will  usually  remove 
the  difficulty. 

Similar  results  may  be  obtained  by  using  picric  acid  instead  of  Orange  G. 

2.  Since  the  sections  are  arranged  serially,  it  is  possible  to  trace  the  course  of  a  vessel 
from  section  to  section;  but  to  obtain  a  complete  picture  of  the  vessels  it  is  necessary  to 
reconstruct  (a)  diagrams  or  (b)  models,     (a)  Where  conditions  are  not  too  complicated  the 
graphic  reconstructions  are  sufficient.     It  is  possible  to  make  a  map,  as  it  were,  of  the  vessels 
on  paper  so  as  to  get  a  comprehensive  view  of  a  whole  system  of  vessels  (see  Appendix), 
(b)  Where  there  are  many  vessels  it  is  best  to  make  plastic  reconstructions.     By  this  method 
any  number  of  vessels  may  be  reproduced  in  wax,  and  a  model  of  an  entire  system  obtained 
(see  Appendix). 


THE   DEVELOPMENT  OF  THE   VASCULAR  SYSTEM.  291 

Where  it  is  possible  to  obtain  living  embryos  of  some  size,  chicks  for  example,  infra 
•vitam  injections  of  the  vessels  afford  instructive  objects  for  study.  While  the  heart  is  still 
beating,  India  ink  is  injected  into  the  liver  by  means  of  a  small  hypodermic  syringe.  The 
ink  is  soon  carried  into  the  vessels.  The  embryo  is  fixed  and  the  tissues  then  rendered  more 
or  less  transparent  by  putting  in  glycerin. 

The  Heart. — Chick  embryos  are  taken  during  the  first  half  of  the  second  day  of  incu- 
bation, fixed  and  sectioned  as  in  the  preparation  for  the  study  of  blood  vessels  (see  above). 
Staining  may  be  done  with  borax -carmin  before  embedding,  or  the  sections  may  be  stained 
with  haematoxylin.  The  double  origin  of  the  heart  is  clearly  demonstrated  in  the  sections 
just  behind  the  head  region. 

Transverse  sections  taken  at  random  through  the  heart  in  later  stages  are  instructive, 
but  for  a  complete  study  recourse  must  be  had  to  serial  sections  and  plastic  reconstructions. 

The  Lymphatics. — In  any  embryo  prepared  for  the  study  of  the  bloodvessels  (see  above) 
the  lymphatic  channels  may  be  seen.  It  must  be  remembered,  however,  that  the  lymphatic 
vessels  do  not  begin  to  develop  for  some  time  after  the  appearance  of  the  blood  vessels 
in  the  embryo.  Frequently  it  is  difficult  to  distinguish  the  lymphatic  channels  from 
veins,  for  both  may  contain  blood  cells. 

Developing  lymph  glands  may  be  studied  in  the  axilla  and  groin  of  foetal  pigs  which  have 
reached  a  length  of  30  mm.  and  more.  Serial  sections  prepared  for  the  study  of  blood 
vessels  (see  above)  may  be  used;  or  the  above  mentioned  regions  may  be  cut  from  the  fresh 
embryo,  fixed  in  Flemming's  fluid,  sectioned  in  paraffin  and  stained  with  Heidenhain's 
haematoxylin. 

Very  recently  an  ingenious  scheme  has  been  devised  for  injecting  the  vessels  in  embryos 
with  India  ink  (H.  McE.  Knower:  A  New  and  Sensitive  Method  of  Injecting  the  Vessels  of 
Small  Embryos,  Etc.,  under  the  Microscope.  Anat.  Record,  Vol.  II,  No.  5,  1908). 

References  for  Further  Study. 

BERNAVS,  A.  C.:  Entwickelungsgeschichte  der  Atrioventricularklappen.  Morph.  Jahr- 
buch,  Bd.  II,  1876. 

BORN,  G.:  Beitrage  zur  Entwicklungsgeschichte  des  Saugetierherzens.  Archiv.  f. 
mik.  Anat.,  Bd.  XXXIII,  1899. 

DISSE,  J.:  Die  Entstehung  des  Blutes  und  der  ersten  Gefasse  im  Hiihnerei.  Arch.  /. 
mik.  Anat.,  Bd.  XVI,  1879. 

ETERNOD,  A.  C.  F.:  Premiers  stades  de  la  circulation  sanguine  dans  1'oeuf  et  embryon 
humain.  Anat.  Anz.,  Bd.  XV,  1899. 

His,  W. :  Anatomic  menschlicher  Embryonen.    Leipzig,  1880-1885.     With  Atlas. 

HOCHSTETTER,  F. :  Die  Entwickelung  des  Blutgefasssystems.  In  Hertwig's  Handbuch 
der  vergleich.  und  experiment.  Entwickelungslehre.  Bd.  Ill,  Teil  II,  1901.  Contains  also 
extensive  bibliography. 

HOWELL,  W.  H. :  The  Life  History  of  the  Formed  Elements  of  the  Blood,  Especially 
the  Red  Blood-corpuscles.  Journal  of  Morph.,  Vol.  IV,  1890. 

HUNTINGTON,  G.  S.:  The  Genetic  Interpretation  of  the  Development  of  the  Mammalian 
Lymphatic  System.  Anat.  Record,  Vol.  II,  Nos.  i  and  2,  1908. 

HUNTINGTON,  G.  S.,  and  McClure,  C.  F.  W.:  Development  of  Postcava  and  Tribu- 
taries in  the  Domestic  Cat.  Am.  Jour,  of  Anat.,  Vol.  VI,  1907. 

HUNTINGTON,  G.  S.:  The  Phylogenetic  Relations  of  the  Lymphatic  and  Blood  Vascular 
Systems  in  Vertebrates.  Anat.  Record,  Vol.  IV,  1910. 

HUNTINGTON,  G.  S.:  The  Genetic  Principles  of  the  Development  of  the  Systemic  Lym- 
phatic Vessels  in  the  Mammalian  Embryo.  Anat.  Record,  Vol.  IV,  1910. 


292  TEXT-BOOK  OF  EMBRYOLOGY. 

HUNTINGTON,  G.  S.:  The  Development  of  the  Lymphatic  System  in  Reptiles.  Anat. 
Record,  Vol.  V,  1911. 

HUNTINGTON,  G.  S.,  and  McClure,  C.  F.  W.:  The  Anatomy  and  Development  of  the 
Jugular  Lymph  Sacs  in  the  Domestic  Cat.  Am.  Jour,  of  Anat.,  Vol.  X,  1910. 

KLING,  C.  A  :  Studien  liber  die  Entwicklung  der  Lymphdriisen  beim  Menschen.  Archiv. 
f.  mik.  Anat.,  Bd.  LXIII,  1904. 

KOLLMANN,  J.:  Handatlas  der  Entwickelungsgeschichte  des  Menschen,  Bd.  II,  1907. 

LEHMAN,  H. :  On  the  Embryonic  History  of  the  Aortic  Arches  in  Mammals.  Anat.  Anz., 
Bd.  XXVI,  1905. 

LEWIS,  F.  T.:.  The  Development  of  the  Vena  Cava  Inferior.  Am.  Jour,  of  Anat.,  Vol.  I, 
1902. 

LEWIS,  F.  T. :  The  Development  of  the  Veins  in  the  Limbs  of  Rabbit  Embryos.  Am. 
Jour,  of  Anat.,  Vol.  V,  1906. 

MALL,  F.  P.:  Development  of  the  Internal  Mammary  and  Deep  Epigastric  Arteries  in 
Man.  Johns  Hopkins  Hosp.  Bull.,  1898. 

MALL,  F.  P.:  On  the  Development  of  the  Blood  Vessels  of  the  Brain  in  the  Human 
Embryo.  Am.  Jour,  of  Anat.,  Vol.  IV,  1905. 

MAXIMOW,  A.:  Die  Fruhesten  Entwicklungsstadien  der  Blut-  und  Bindegewebszellen 
beim  Saugetierembryo,  bis  zum  Anfang  der  Blutbildung  in  der  Leber.  Arch.  f.  mik.  Anat., 
Bd.  LXXIII,  1909. 

MAXIMOW,  A.:  Lymphozyt  als  gemeinsame  Stammzelle  der  verschicdenen  Blutelemente  in 
der  embryonalen  Entwicklung  und  im  postfetalen  Leber  der  Saugetiere.  Folia  Hdmatolog., 
Bd.  VIII,  1909. 

MAXIMOW.  A.:  Die  embryonale  Histogenese  des  Knochenmarks  der  Saugetiere.  Arch, 
f.  mik.  Anat.,  Bd.  LXXVI,  1910. 

MINOT,  C.  S.:  On  a  Hitherto  Unrecognized  Form  of  Blood  Circulation  without  Capil- 
laries in  the  Organs  of  Vertebrata.  Proc.  Boston  Soc.  Nat.  Hist.,  Vol.  XXIX,  1900. 

ROSE,  C.:  Zur  Entwickelungsgeschichte  des  Saugetierherzens.  Morph.  Jahrbuch,  Bd. 
XV,  1889. 

RUCKERT,  J.,  and  MOLLIER,  S.:  Die  erste  Entstehung  der  Gefasse  und  des  Blutes  bei 
Wirbeltiere.  In  Hertwig's  Handbuch  der  vergleich  und  experiment.  Enluickelungslehre, 
Bd.  I,  Teil  I,  1906.  Contains  also  extensive  bibliography. 

SABIN,  F.  ,R.:  On  the  Origin  of  the  Lymphatic  System  from  the  Veins  and  the  Develop- 
ment of  the  Lymph  Hearts  and  Thoracic  Duct  in  the  Pig.  Am.  Jour,  of  Anat.,  Vol.  I,  1902. 

SALA,  L.:  Svilluppo  dei  cuori  linfatici  e  dei  dotti  toracici  nell'  embrione  di  polio. 
Ricerche  fatte  nel  laboratorio  de  anatomia  ncrmale  della  R.  Universita  di  Roma.  Vol.  VII,  1900. 

STOERK,  O.:  Uber  die  Chromreaktion  der  Glandula  coccygea  und  die  Beziehung  dieser 
Driise  zum  Nervus  sympthathicus.  Arch.  f.  mik.  Anat.,  Bd.  LXIX,  1906. 

STOHR,  P.:  Uber  die  Entwicklung  der  Darmlymphknotchen  und  uber  die  Ruckbildung 
von  Darmdrusen.  Arch.  f.  mik.  Anat.,  Bd.  LI,  1898. 

TANDLER,  J.:  Zur  Entwickelungsgeschichte  der  menschlichen  Darmarterien.  Anat. 
Heft,  Bd.  XXIII,  1903. 

TONKOFF,  W. :  Die  Entwickelung  der  Milz  bei  den  Amnioten.  Archiv.  f.  mik.  Anat., 
Bd.  LVI,  1900. 

WEIDENREICH,  F. :  Die  Morphologic  der  Blutzellcn  und  ihre  Beziehungen  zu  einander. 
Anat.  Record,  Vol.  IV,  1910. 

WRIGHT,  J.  H.:  The  Origin  and  Nature  of  the  Blood  Plates.  Boston  Med.  and  Surg. 
Jour.,  Vol.  CLIV,  1906. 


CHAPTER  XI 
THE  DEVELOPMENT  OF  THE  MUSCULAR  SYSTEM. 

Anatomy  and  Histology  show  that  there  are,  in  a  sense,  two  muscular 
systems  in  the  body,  and  Embryology  teaches  that  the  two  systems  have  dif- 
ferent origins. 

1.  The  skeletal  musculature. — This,  as  the  name  indicates,  is  closely  associated 
with  the  skeletal  system.     It  is  made  up  of  striated  muscle  fibers  arranged  to 
form  definite  bundles  or   muscles.     The  skeletal   musculature  is  under  the 
voluntary  control  of  the  central  nervous  system. 

2.  The  visceral  musculature. — This  is  found  in  connection  with  and  forms 
integral  parts  of  certain  organs.     It  is  made  up  of  two  different  kinds  of  fibers — 
smooth  muscle  fibers  or  cells  and  striated  fibers  or  cells  (heart-muscle  cells). 
The  latter  are  found  only  in  the  wall  of  the  heart.     The  visceral  musculature  is 
involuntary,  being  under  the  control  of  the  sympathetic  nervous  system. 

Both  systems  are  derived  from  mesoderm  but  from  distinct  parts  of  the 
mesoderm.  Furthermore,  their  developmental  histories  are  quite  different,  as 
will  be  seen  in  the  following  paragraphs. 

THE  SKELETAL  MUSCULATURE. 

In  the  chapter  on  the  development  of  the  germ  layers  it  was  said  (p.  72) 
that  throughout  the  length  of  the  body  region  of  the  embryo  the  mesoderm  on 
each  side  of  the  neural  tube  and  notochord  becomes  divided  into  a  definite 
number  of  segments — the  primitive  segments  or  mesodermic  somites  (Figs.  57, 
72,  74).  These  indicate  the  segmentation  of  the  body,  and  the  history  of  the 
greater  part  of  the  skeletal  musculature  dates  from  their  differentiation  from 
the  axial  mesoderm.  Thus  the  skeletal  musculature  is,  for  the  most  part, 
primarily  segmental  in  character. 

At  first  the  primitive  segments  are  composed  of  closely  packed,  epithelial- 
like  cells,  and  each  segment  contains  a  small  cavity  which  represents  a  portion 
of  the  ccelom  (Fig.  141).  The  ventro-medial  parts  of  the  segments  become 
differentiated  to  form  the  sderotomes  which  are  composed  of  more  loosely  ar- 
ranged cells  (Fig.  261),  and  which  are  destined  to  give  rise  to  the  vertebrae  and 
to  the  various  kinds  of  connective  tissue  in  their  neighborhood.  The  lateral 
parts  of  the  segments  become  differentiated  to  form  the  cutis  plates  which  are 
destined  to  give  rise  to  a  part  of  the  corium  of  the  skin.  The  remaining  portions 

293 


294 


TEXT-BOOK  OF  EMBRYOLOGY. 


of  the  segments  form  the  muscle  plates  or  myotomes  (Fig.  261),  from  which 
develop  by  far  the  greater  part,  at  least,  of  the  voluntary  striated  muscles. 

The  differentiation  of  the  parts  of  the  primitive  segments  begins  in  the  cervi- 
cal region  by  the  end  of  the  second  week,  and  then  gradually  proceeds  toward 
the  tail.  Three  myotomes  are  also  probably  formed  in  the  occipital  region. 
The  cells  of  the  myotomes  are  at  first  of  an  epithelial  character  (Fig.  143). 
Contractile  fibrils  appear  in  the  cells  and  the  latter  are  transformed  directly 
into  muscle  fibers.  (For  histogenesis  see  p.  307).  The  fibers  later  alter  their 
direction  in  accordance  with  the  particular  muscle  to  which  they  belong.  The 
muscle  tissue  first  formed  is  thus  segmented,  being  derived  from  the  segmen- 


Neural  crest 


— Myotome 


Sclerotome 


Pronephros , 


Parietal  mesoderm — 
Intestine 


l     Upper 

~      limbbud 


Visceral  mesoderm  - 


FIG.  261. — Transverse  section  of  human  embryo  of  the  3rd  week.     Scl.1,  Break  in  myotome  at 
point  where  sclerotome  is  closely  attached.     Kollmann. 

tally  arranged  myotomes,  but  as  development  proceeds  the  myotomes  undergo 
extensive  changes  by  which  the  segmental  character  is  lost  in  the  majority  of 
cases.  It  is  retained,  however,  in  a  few  instances,  such  for  example  as  the 
intercostal  muscles.  The  course  of  the  changes  which  obliterate  the  segmental 
character  of  the  myotomes  and  give  rise  to  the  various  muscles  has  not  been 
observed  in  all  cases.  But  since  a  nerve  belonging  to  any  particular  segment 
and  innervating  the  myotome  of  that  segment  always  innervates  the  muscles 
derived  from  that  myotome,  it  is  possible  to  learn  something  of  the  history  of 
the  myotomes  by  studying  the  innervation  of  the  muscles. 

From  a  consideration  of  what  is  known  concerning  the  individual  histories 


THE   DEVELOPMENT  OF  THE   MUSCULAR  SYSTEM.  295 

of  the  muscles  and  concerning  the  innervation  of  the  muscles,  certain  factors 
can  be  recognized,  to  one  or  more  of  which  the  changes  in  the  myotomes  may 
be  referred.  These  factors  are  as  follows: 

1.  Migration. — The  myotomes  may  migrate  in  whole  or  in  part,  and  the 
muscles  derived  from  them  may  be  situated  far  beyond  their  limits.    For 
example,  the  latissimus  dorsi  is  derived  from  cervical  myotomes  but  ultimately 
becomes  attached  to  the  lumbar  vertebrae  and  to  the  crest  of  the  ilium.     To  this 
factor,  possibly  more  than  to  any  other,  is  due  the  loss  of  the  segmental  character 
in  the  musculature. 

2.  Fusion. — Portions  of  two  or  more  myotomes  may  fuse  to  form  one  muscle. 
For  example,  each  oblique  abdominal  muscle  is  derived  from  several  thoracic 
myotomes. 

3.  Longitudinal  Splitting. — Very  frequently  a  myotome  or  a  developing 
muscle  splits  longitudinally  into  two  or  more  portions.     The  sternohyoid  and 
the  omohyoid,  for  example,  are  formed  in  this  manner. 

4.  Tangential  Splitting. — A  developing  muscle  may  split  tangentially  into 
two  or  more  plates  or  layers.     The  two  oblique  and  the  transverse  abdominal 
muscles,  for  example,  are  formed  in  this  way. 

5.  Degeneration. — Myotomes  may  degenerate  as  a  whole  or  in  part  and  be 
converted  into  some  form  of  connective  tissue,  such  as  fascia,  ligament  or 
aponeurosis.     The   aponeuroses   of   the   transverse   and   oblique   abdominal 
muscles  are  probably  due  to  a  degeneration  of  portions  of  the  myotomes  from 
which  the  muscles  are  derived. 

6.  Change  of  Direction. — The  muscle  fibers  may  change  their  direction. 
As  a  matter  of  fact,  the  fibers  of  very  few  muscles  retain  their  original  direction. 

Muscles  of  the  Trunk. 

The  myotomes  are  at  first  arranged  serially  along  each  side  of  the  notochord  and 
spinal  cord  (compare  Fig.  262  with  Figs.  143  and  261).  By  the  end  of  the  second 
week  fourteen  myotomes  are  differentiated  in  the  human  embryo.  Differen- 
tiation continues  until,  by  the  end  of  the  fourth  week,  the  total  number — thirty- 
eight — is  present.  Of  the  thirty-eight,  three  are  occipital,  eight  cervical,  twelve 
thoracic,  five  lumbar,  five  sacral,  and  five  (or  six)  coccygeal.  The  occipital 
myotomes  are  transient  structures  that  appear  in  relation  with  the  hypoglossal 
(XII)  nerve.  The  cervical,  thoracic,  lumbar,  sacral  and  coccygeal  myotomes 
correspond  individually  to  the  spinal  nerves  (Fig.  262).  As  stated  on  page  184, 
the  myotomes  alternate  with  the  anlagen  of  the  vertebrae.  Consequently  in  the 
cervical  region  there  are  eight  myotomes,  corresponding  to  the  eight  cervical 
spinal  nerves,  and  only  seven  vertebrae.  The  myotomes  in  the  neck  and  body 
regions  are  destined  to  give  rise  to  the  dorsal  musculature,  to  the  thoraco- 


296 


TEXT-BOOK  OF  EMBRYOLOGY. 


abdominal  musculature,  to   a   part  of  the  muscles  of  the  neck,  and  to  the 
muscles  of  the  tail  region.     There  is  a  possibility  that  they  give  rise  also  to  the 


muscles  of  the  tongue. 


As  the  myotomes  continue  to  develop,  they  become  elongated  in  a  ventral 


FIG.  262. — Lateral  view  of  human  embryo  of  9  mm.  (4^  weeks).     Bardeen  and  Lewis. 

The  area  from  which  the  skin  has  been  removed  is  drawn  from  reconstructions.  The  myotomes 
have  fused  to  a  certain  extent,  so  that  segmentation  is  becoming  less  distinct.  Note  that  the 
myotomes  correspond  to  the  spinal  nerves.  The  developing  muscle  mass  (the  myotomes 
collectively)  extends  ventrally  in  the  body  wall  in  the  thoracic  region,  and  is  divided  by  a 
longitudinal  groove  into  two  parts — a  dorsal  and  a  ventro-lateral  (see  text). 

In  the  region  of  the  upper  extremity,  dense  masses  of  "  premuscle  "  tissue  are  represented  which 
later  form  the  muscles.  In  the  region  of  the  forearm  and  hand  the  "  premuscle  "  tissue  has 
been  removed  to  disclose  the  anlagen  of  the  skeletal  elements  (radius,  ulna,  and  hand  plate). 
In  the  region  of  the  lower  extremity  the  superficial  tissue  has  been  removed  to  disclose  the 
border  vien,  the  anlagen  of  the  os  coxae,  and  the  lumbo-sacral  nerve  plexus. 


direction.  Those  of  the  thoracic  region  extend  into  the  connective  tissue  of 
the  somatopleure,  or  in  other  words,  into  the  lateral  body  walls  (compare 
Figs.  262  and  263).  During  the  fifth  week  the  myotomes  give  rise  to  a  dorso- 
ventral  mass  of  developing  muscle  tissue,  in  which  the  segmental  character 


THE   DEVELOPMENT  OF  THE   MUSCULAR  SYSTEM. 


297 


Spinal  ganglion 


Dorsal  musculature 


Ventro-lateral 
musculature 


Vertebral  arch 
Dorsal  ramus  of 
spinal  nerve 


Scgmental  artery 

Costal  process 

Lat.  branch  of 
nal  nerve 

Vent,  branch  of 
ipinal  nerve 


FIG.  263. — Diagrammatic  cross  section  through  the  5th-6th  thoracic  segments  of  a  human  embryo 
of  9  mm.  (4^  weeks).     Bardeen  and  Lewis. 


FIG.  264. — Drawing  from  a  reconstruction  of  the  region  of  the  lower  extremity  of  a  human  embryo 
of  9  mm.  (4%  weeks).  Bardeen  and  Lewis. 

The  visceral  organs  and  the  greater  part  of  the  left  body  wall  have  been  removed.  The  8th  thoracic 
to  the  5th  sacral  segments  are  shown.  On  the  right  side  of  the  body  the  costal  processes, 
the  spinal  nerves  (including  the  lumbo-sacral  plexus),  and  the  lower  extremity  are  shown. 
On  the  left  side  the  costal  processes,  the  spinal  nerves,  and  the  nth  and  i2th  thoracic  myo- 
tomes  are  represented.  Note  the  dorsal,  lateral,  and  sympathetic  branches  of  the  spinal 
nerves. 


298 


TEXT-BOOK  OF  EMBRYOLOGY. 


largely  disappears.     The  muscle  mass  then  becomes  divided  longitudinally 
into  two  parts,  (i)  a  dorsal  and  (2)  a  ventro-lateral  (Figs.  262,  263  and  264). 

1.  The  dorsal  part  is  destined  to  give  rise  to  those  dorsal  muscles  of  the 
trunk  that  are  not  associated  with  the  extremities,  and  is  innervated  by  the 
dorsal  rami  of  the  spinal  nerves  (Fig.  263). 

2.  The  ventro-lateral  part  again  divides  longitudinally  into  (a)  a  lateral 


ernal  oblique 

ernal  intei  costal 

ernal  intercostal     '  Ventro-lateral 

ernal  oblique  I  musculature 

nsversalis 

tus 


FIG.  265. — Diagrammatic  cross  section  through  the  6th-yth  thoracic  segments  of  a  human  embryo 
of  17  mm.  (5J  weeks).     Bardeen  and  Lewis. 

and  (b)  a   ventral  part,  although  the  line  of   division  is  not  so  distinct  as 
between  the  original  (i)  dorsal  and  (2)  ventro-lateral  parts  (Fig.  265). 

(a)  The  lateral  part  subdivides  tangentially  and  gives  rise  in  the  cervical 
region  to  the  longus  capitis,  longus  colli,  rectus  capitis  anterior,  to  the 
scaleni,  and  to  parts  of  the  trapezius  and  sternomastoideus  (Figs.  266 
and  267).  In  the  thoracic  region  it  gives  rise  to  the  intercostales 
and  to  the  transversus  thoracis  (Figs.  265  and  268) ;  in  the  abdominal 
region  to  the  psoas,  quadratus  lumborum,  and  to  the  obliqui  and 
transversus  abdominis  (Figs.  267  and  268). 


THE   DEVELOPMENT  OF  THE  MUSCULAR  SYSTEM. 


299 


(b)  The  ventral  part  gives  rise  in  the  cervical  region  to  the  sternohyoideus, 
omohyoideus,  sternothyreoideus  and  geniohyoideus.  In  the  abdominal 
region  the  ventral  part  gives  rise  to  the  rectus  abdominis  and  to  the 
pyramidalis  (Figs.  265  and  267).  In  the  thoracic  region  there  are  no 
muscles  derived  from  the  ventral  part,  corresponding  to  those  in  the 
abdominal  region.  This  is  probably  due  to  the  development  of  the 
sternum. 


FIG.  266. — Lateral  view  of  a  human  embryo  of  n  mm.  (about  5  weeks).  Bardeen  and  Lewis. 
The  area  from  which  the  skin  has  been  removed  is  drawn  from  reconstructions.  The  dorsal  mus- 
culature has  been  removed  from  the  region  of  the  upper  extremity,  exposing  the  4th  to  the 
8th  cervical  and  the  ist  to  the  3d  thoracic  vertebrae.  The  dorsal  musculature  has  likewise 
been  removed  from  the  5th  lumbar  and  first  three  sacral  segments.  Segmentation  is  practi- 
cally lost  in  the  dorsal  musculature  in  the  thoracic  region,  but  is  still  evident  in  the  lumbar, 
sacral  and  coccygeal  regions.  The  ventro-lateral  musculature  is  distinctly  separated  from  the 
dorsal,  and  is  beginning  to  differentiate  into  the  muscles  of  the  thorax  and  abdomen. 

The  ventro-lateral  portions  of  the  lumbar  myotomes  and  of  the  first  two 
sacral  myotomes,  corresponding  to  the  ventro-lateral  portions  of  the  thoracic 
myotomes,  apparently  do  not  take  part  in  the  production  of  muscles  which  be- 
long to  the  body  wall  proper.  It  is  even  questionable  whether  they  give  rise  to 
any  muscles  of  the  lower  extremities.  The  ventro-lateral  portions  of  the  third 


300 


TEXT-BOOK  OF  EMBRYOLOGY. 


and  fourth  sacral  myotomes  give  rise  to  the  levator  ani,  the  coccygeus,  the 
sphincter  ani  externus  and  the  perineal  muscles.  The  dorsal  parts  of  the  myo- 
tomes as  far  as  the  fifth  sacral  probably  give  rise  to  the  sacrospinalis  (Fig.  266). 
THE  DIAPHRAGM. — In  addition  to  certain  structures  which  are  considered 
in  connection  with  the  pericardium  (parietal  mesoderm,  mesocardium  and 
common  mesentery — Chapter  XIV),  two  myotomes  on  each  side  enter  into 


FlG.  '267. — Drawing  from  a  reconstruction  of  a  human  embryo  of  20  mm.  (about  7  weeks). 

Bardcen  and  Lewis. 

The  superficial  tissues  have  been  removed  from  the  extremities,  the  body  wall,  and  the  back. 

the  formation  of  the  diaphragm.  These  are  the  third  and  fourth  cervical  myo- 
tomes, parts  of  which  grow  into  the  developing  diaphragm  in  the  earlier  stages 
when  it  is  situated  far  forward  in  the  cervical  region  (p.  378  and  Fig.  336),  and 
give  rise  to  its  muscular  elements. 

Muscles  of  the  Head. 

Primitive  segments  (mesodermic  somites)  are  not  clearly  demonstrable  in 
the  heads  of  human  embryos,  nor,  in  fact,  in  the  heads  of  any  of  the  higher 
Vertebrates.  In  some  of  the  lower  forms,  however,  they  are  very  distinct.  It 
seems  possible,  even  probable,  that  their  indistinctness  in  the  higher  animals 


THE   DEVELOPMENT  OF  THE   MUSCULAR  SYSTEM. 


301 


is  due  to  an  abbreviation  or  condensation  in  the  development  of  the  head 
region.  Such  condensations  are  known  to  occur  in  the  development  of  other 
structures.  In  a  human  embryo  3.5  mm.  long,  three  structures  resembling 
segments  have  been  seen  somewhat  caudal  to  the  region  of  the  ootic  vesicle  on 


FIG.  268. — Drawing  from  a  reconstruction  of  the  right  side  of  a  human  embryo  of  20  mm.  (about 

7  weeks).  Bardeen  and  Lewis. 

The  left  body  wall  and  viscera  have  been  removed.  Note  especially  the  following  muscles:  The 
deltoid  and  biceps,  just  to  the  left  of  the  brachial  plexus  and  below  the  clavicle;  the  internal 
intercostals;  the  diaphragm,  attached  to  the  body  wall;  the  transverse  abdominal  and  the 
rectus  abdominis;  the  quadratus  lumborum,  just  to  the  right  of  the  transverse  abdominal; 
the  psoas,  cut  just  above  the  lumbo-sacral  plexus;  the  levator  ani,  running  obliquely  upward 
from  the  coccygeal  region. 


one  side.  On  the  other  side  there  were  seven  similar  but  smaller  structures. 
All  were  composed  of  epithelial-like  cells  surrounding  small  cavities. 
Whether  these  segment-like  structures  bear  any  relation  to  the  mesenchymal 
condensations  which  appear  regularly  in  the  occipital  region  (p.  193),  seems 
not  to  have  been  determined. 


302 


TEXT-BOOK  OF  EMBRYOLOGY. 


Although  the  transformation  of  head  segments  into  muscles  has  not  been 
followed  in  detail  in  mammalian  embryos,  it  may  be  inferred  from  the  study  of 
lower  forms  that  three  segments  are  involved  in  the  formation  of  the  eye  muscles. 
The  most  cephalic  (anterior)  segment  gives  rise  to  the  recti  superior,  inferior 
and  mediates  (internus)  and  to  the  obliquus  inferior,  all  of  which  are  innervated 
by  the  occulomotor  (III)  nerve.  The  next  segment  gives  rise  to  the  obliquus 
superior  which  is  innervated  by  the  pathetic  (IV)  nerve.  The  most  caudal 
segment  gives  rise  to  the  reclus  lateralis  (externus)  which  is  innervated  by  the 
abducens  (VI)  nerve. 

The  development  and  innervation  of  the  other  muscles  of  the  head  and  of 
the  hyoid  musculature  present  certain  peculiarities  which  have  caused  these 
muscles  to  be  considered  as  more  closely  related  to  the  visceral  musculature 
than  to  the  myotomic  musculature.  In  the  first  place  they  are  derived  from 


Eighth  cervical 

myotome 


Somatopleure 

Mesonephric 
duct 


FIG.  269. — Transverse  section  through  the  eighth  cervical  segment  of  a  human 
embrvo  of  2.1  mm.     Lewis, 


the  branchial  arches  (hence  are  often  called  branchiomeric  muscles'),  and  not 
directly  from  the  myotomes  of  the  neck  region.  This  places  them  in  closer 
relation  to  the  visceral  muscles,  although  they  are  structurally  and  functionally 
different  from  the  latter.  In  the  second  place  the  nerves  which  supply  them 
are  fundamentally  different  from  those  which  supply  the  myotomic  muscles 
(Chap.  XVII). 

The  first  branchial  arch  on  each  side  gives  rise  to  the  temporalis,  masseter 
and  pterygoidei,  to  the  mylohyoideus  and  digastricus  (venter  anterior)  and  to  the 
tensor  tympani  and  tensor  -veli  palatini.  All  these  muscles  are  innervated  by  the 
trigeminal  (V)  nerve. 

The  second  arch,  which  is  often  called  the  hyoid  arch,  gives  rise  to  a  large 
sheet  of  myogenic  tissue  which  produces  many  of  the  facial  muscles,  such  as  the 


THE  DEVELOPMENT   OF  THE   MUSCULAR  SYSTEM.  303 

platysma  and  epicranius,  the  muscles  of  expression — quadratus  labii  superwris, 
risorius,  triangularis,  mentalis,  etc.;  also  two  muscles  connected  with  the  hyoid 
bone — digastricus  (venter  posterior)  and  stylohyoideus — and  the  stapedius  of  the 
middle  ear.  The  facial  (VII)  nerve  corresponds  to  the  second  arch  and  sup- 
plies all  these  muscles. 

The  glossopharyngeal  (IX)  nerve  corresponds  to  the  third  branchial  arch, 
and  this  fact  indicates  the  muscles  derived  from  that  arch.  Some,  at  least,  of 
the  constrictor  muscles  of  the  pharynx  are  derived  from  the  third  arch.  The 
stylo-pharyngeus  is  also  a  derivative  of  the  same  arch. 

The  vagus  (X)  nerve  is  associated  with  the  fourth  and  fifth  arches  and  con- 
sequently innervates  the  muscles  derived  from  these  arches,  viz.,  the  rest  of  the 
constrictors  of  the  pharynx  (see  above),  the  laryngeal  muscles  and  the  muscles 
of  the  soft  palate  (except  the  tensor  veli  palatini  which  is  derived  from  the  first 
arch  (p.  302) .  The  glossopalatinus  and  chondroglossus  are  also  derived  from 
the  fourth  and  fifth  arches,  while  the  rest  of  the  extrinsic  muscles  of  the  tongue 
are  of  myotomic  origin. 

Two  other  muscles  are  probably  derived  in  part  from  the  branchial  arches, 
for  fibers  of  the  spinal  accessory  (XI)  nerve  afford  a  part  of  their  innervation. 
These  are  the  trapezius  and  the  sternomastoideus,  the  remaining  parts  of  which 
are  of  myotomic  origin  (p.  298). 

Muscles  of  the  Extremities. 

The  question  as  to  whether  the  muscles  of  the  extremities  are  derivatives  of 
the  myotomes  or  of  the  mesenchymal  tissue  in  the  limb  buds  has  not  been 
settled.  In  some  of  the  lower  Vertebrates,  especially  in  some  of  the  Fishes,  it 
seems  to  have  been  pretty  clearly  demonstrated  that  bud-like  processes  from 
the  myotomes  grow  into  the  anlagen  of  the  extremities  (fins),  and  there  give 
rise  to  muscles.  In  other  lower  forms  no  such  buds  from  the  myotomes  have 
been  demonstrated,  but  the  muscles  are  apparently  derived  directly  from 
the  mesenchymal  tissue  in  the  anlagen  of  the  extremities.  In  the  higher  verte- 
brates, especially  in  Mammals,  no  distinct  myotome  buds  have  been  traced  into 
the  extremities.  Some  investigators  hold,  however,  that  instead  of  myotome 
buds  some  cells  from  the  myotomes — myoblasts — wander  into  the  limb  buds 
and  give  rise  to  muscles.  Other  investigators  are  inclined  to  the  view  that  the 
musculature  of  the  extremities  is  not  of  myotomic  origin,  but  that  it  is  derived 
from  the  mesenchymal  tissue  of  the  limb  buds. 

A  most  striking  feature  of  the  musculature  of  the  extremities  is  its  distinctly 
segmental  nerve  supply.  This,  of  course,  is  in  favor  of,  although  it  does  not 
prove,  its  myotomic  origin.  If  the  muscles  of  the  extremities  are  of  myotomic 
origin,  it  is  very  probable  that  several  myotomes  take  part  in  their  formation. 


304 


TEXT-BOOK  OF  EMBRYOLOGY. 


In  the  first  place  among  the  lower  Vertebrates  the  muscles  of  each  extremity  are 
derived  from  several  myotomes  and  are  innervated  by  segmental  nerves  cor- 
responding to  these  myotomes.  In  the  second  place  among  the  higher  Verte- 
brates, although  the  myotomic  origin  of  the  muscles  has  not  been  clearly  demon- 
strated, the  nerve  supply  in  each  extremity  comes  through  several  segmental 
spinal  nerves. 

Knowledge  concerning  the  development  of  the  individual  muscles  of  the  ex- 
tremities in  the  human  embryo  is  incomplete.  Especially  is  this  true  of  the 
muscles  of  the  lower  extremities. 

The  upper  limb  bud  first  appears  in  embryos  of  2-3  mm.  (during  the  third 
week)  as  a  slight  swelling  ventro-lateral  to  the  myotomes  in  the  lower  cervical 


Upper  limb  bud 


w  / 

Border  vein      /}•'& 

a?     * 

I-*!-1.    Somatopleure 

FIG.  270. — Transverse  section  through  the  eighth  cervical  segment  of  a  human 
embryo  of  4.5  mm.     Lewis. 

region  (Fig.  269;  see  also  Fig.  123).  The  swelling  gradually  enlarges  and  by 
the  time  the  embryo  has  reached  a  length  of  4-5  mm.  lies  opposite  the  last  four 
cervical  and  the  first  thoracic  myotomes.  At  this  time  it  is  filled  with  closely 
packed  mesenchymal  cells.  No  buds  from  the  myotomes  can  be  seen  extending 
into  the  mesenchyme  (Fig.  270). 

In  succeeding  stages  the  limb  bud  enlarges  still  more,  and  the  mesenchymal 
tissue  becomes  denser  (Figs.  271  and  272).  During  these  stages  no  growths, 
either  of  buds  or  of  individual  cells,  from  the  myotomes  are  apparent.  Some 
of  the  cervical  nerves,  however,  enter  the  limb  buds  (Fig.  272). 

Apparently  the  tissue  from  which  the  muscles,  as  well  as  the  skeletal  ele- 
ments, are  to  develop,  is  the  condensed  mesenchymal  tissue.  The  first  indica- 
tion of  differentiation  occurs  during  the  fourth  week  (embryo  of  about  8  mm.). 
The  central  portion  or  core  of  the  mesenchymal  mass  becomes  still  denser  to 
form  the  anlage  of  the  skeletal  elements  of  the  extremity.  The  tissue  of  the 


THE   DEVELOPMENT  OF  THE   MUSCULAR  SYSTEM. 


305 


core  shades  off  into  the  surrounding  tissue  of  a  lesser  density,  which  is  destined 
to  give  rise  to  the  muscles  and  which  is  known  as  the  premuscle  sheath. 

During  these  processes  of  differentiation  in  the  limb  bud  proper,  masses  of 
premuscle  tissue  have  also  become  differentiated  around  the  base  of  the  limb 
bud.  These  are  the  forerunners  of  certain  extrinsic  muscles  of  the  upper  ex- 
tremity, such  as  the  pectoralis,  levator  scapula,  trapezius,  latissimus  dorsi,  ser- 
ratus,  etc.  (Fig.  273;  compare  with  Fig.  274). 


Spinal  ganglion 


Intervertebral  disk 


cal 


Upper 
limb  bud 


Border  vein 


FiG.  271. — Transverse  section  through  the  8th  cervical  segment  of  a  human 
embryo  of  5  mm.     Lewis. 

By  the  end  of  the  fifth  week  the  premuscle  sheath  in  the  limb  bud  proper  be- 
comes more  or  less  differentiated  into  muscles  or  groups  of  muscles.  The 
differentiation  is  most  complete  at  the  proximal  end.  From  this  the  transition 
is  gradual  to  the  distal  end  where  the  premuscle  sheath  is  intact. 

By  the  end  of  the  sixth  week  most  of  the  muscles  of  the  upper  extremity  are 
recognizable  (Figs.  274  and  275). 

By  the  end  of  the  seventh  week  practically  all  the  muscles  can  be  recognized 
and  are  composed  of  muscle  fibers. 

During  the  differentiation  of  the  muscles,  the  limb  bud  and  certain  ex- 
trinsic muscles  migrate  a  considerable  distance  caudally.  For  example,  the 


306 


TEXT-BOOK  OF  EMBRYOLOGY. 


pectoralis  and  latissimus  dorsi  migrate  from  the  base  of  the  arm  to  the  thoracic 
wall.  Their  nerves  are  naturally  pulled  with  them.  The  trapezius  muscle, 
which  originates  well  forward  in  the  cervical  region,  migrates  so  that  it  finally 
reaches  as  far  as  the  last  thoracic  vertebra.  The  sternomastoideus  also  origi- 
nates well  forward  in  the  cervical  region,  but  finally  extends  to  the  clavicle  and 
sternum.  The  migration  of  the  upper  extremity  causes  the  brachial  plexus  to 
have  a  caudal  inclination. 

The  lower  limb  buds  arise  very  soon  after  the  upper.     As  stated  on  page  1 53, 
the  upper  limbs  always  maintain  a  slight  advance  over  the  lower  in  develop- 


SP 


6th 
Co 


rvertebral  disk 


FIG.  272. — Transverse  section  through  the  8th  cervical  segment  of  a  human 
embryo  of  7  mm.  (about  4  weeks).     Lewis. 


ment.  As  in  the  case  of  the  upper,  the  lower  limb  buds  appear  as  swellings  on 
the  ventro-lateral  surface  of  the  body,  opposite  the  fifth  lumbar  and  first  sacral 
myotomes.  The  interior  of  each  swelling  is  at  first  composed  of  closely  packed 
mesenchymal  tissue,  but  whether  any  part  of  the  myotomes  enters  it  is  question- 
able. At  all  events  several  spinal  nerves  do  enter  the  tissue  and  supply  the 
muscles.  The  differentiation  of  a  central  core  as  the  anlage  of  the  skeleton,  and 
the  differentiation  of  the  surrounding  tissue  as  the  premuscle  sheath,  take  place 
in  the  same  manner  as  in  the  upper  extremity  (p.  305) .  From  this  premuscle 
sheath  all  the  muscles  of  the  lower  extremity  are  developed. 


THE  DEVELOPMENT  OF  THE  MUSCULAR  SYSTEM.  307 

Histogenesis  of  Striated  Voluntary  Muscle  Tissue. 

The  majority  of  the  striated  voluntary  muscles  of  the  body  are  derived  from 
the  myotomes.  Some  are  derived  from  the  mesenchymal  tissue  in  the  branchial 
arches,  some  possibly  from  the  mesenchymal  tissue  in  the  limb  buds.  The 
primitive  segments  are  at  first  composed  of  closely  arranged,  epithelial-like  cells 
that  radiate  from  a  small  centrally  placed  cavity  (Fig.  141).  The  cavity  repre- 
sents part  of  the  ccelom  and  from  this  point  of  view  it  can  be  said  that  the  muscle 
is  a  derivative  of  the  epithelial  lining  of  the  ccelom.  A  part  of  each  primitive 


5th  nerve 

Phrenic  nerve 
Brachial  plexus 

Sympathetic 

Diaphragm 

Vertebra 


Border  vein 


4th  rib 


FIG.  273. — Drawing  from  a  reconstruction  of  the  upper  limb  region  of  a  human 

embryo  of  9  mm.  (4 J  weeks) ;  ventral  view.     Lewis. 

Inf.  hy.,  infrahyoid;  Lev.  scap.,  levator  scapulae;  My.,  myotome  mass;  Rhom., 
rhomboid;  Trap.,  trapezius. 


segment  becomes  the  sclerotome  and  cutis  plate.     The  remaining  part  be- 
comes the  myotome  or  muscle  plate  (Fig.  261). 

The  cells  of  the  myotome  are  at  first  not  essentially  different  from  those  of 
the  rest  of  the  primitive  segment.  Soon,  however,  changes  take  place  in  them 
and  they  become  the  so-called  myoblasts  or  muscle-forming  cells,  which  are 
destined  to  give  rise  to  the  muscle  fibers.  Opinions  differ  as  to  the  manner  in 
which  the  myoblasts  produce  the  muscle  fibers.  It  was  once  thought  that  each 
myoblast  gave  rise  to  a  single  muscle  fiber  in  which  there  were  several  nuclei,  all 


308 


TEXT-BOOK  OF  EMBRYOLOGY. 


derived  from  the  original  myoblast  nucleus  by  mitotic  division.  It  was  also 
thought  that  the  muscle  fibrillas  represented  highly  modified  and  specialized 
parts  of  the  cytoplasm,  which  arranged  themselves  longitudinally  in  the  cell. 
Some  of  the  later  researches  indicate  that  a  muscle  fiber  represents  a  number  of 
myoblasts  fused  together.  This  explanation  is  not,  however,  accepted  by  all 
investigators. 

In  contrast  with  the  above,  there  is  a  quite  general  consensus  of  opinion  in 
regard  to  the  development  of  the  internal  structure  of  the  muscle  fiber.  •  In  the 


FIG.  274. — Lateral  view  of  a  reconstruction  of  the  muscles  of  the  upper  extremity  of  a  human 
embryo  of  16  mm.  (about  6  weeks).  Lewis. 

The  trapezius  is  the  large  muscle  arising  from  the  transverse  processes  of  the  vertebrae  (at  the  right 
of  the  figure)  and  converging  to  its  insertion  on  the  clavicle.  Just  below  the  insertion  of  the 
trapezius  is  the  deltoid,  which  partly  hides  the  subscapular  (on  the  right)  and  the  pectoralis 
major  (on  the  left).  Arising  beneath  the  deltoid  and  running  downward  to  the  elbow  is  the 
triceps.  To  the  right  of  the  triceps  is  the  teres  major  (composed  of  two  parts).  The  large 
sheet  of  muscle  extending  down  the  forearm  and  sending  divisions  to  the  2d,  30!,  4th  and  5th 
digits  is  the  extensor  communis  digitorum. 


cytoplasm  of  the  myoblasts  there  appear  granules  which  soon  arrange  them- 
selves in  parallel  rows  and  unite  to  form  slender  thread-like  fibrils  (Fig.  276). 
These  fibrils  are  at  first  confined  to  one  myoblast  area.  If  several  myoblasts 
fuse,  the  fibrils  probably  extend  in  a  short  time  from  one  myoblast  area  to 
another.  If  one  myoblast  produces  a  fiber,  the  fibrils  naturally  are  confined  to 
a  single  myoblast  area  throughout  development.  The  fibrils  are  usually 
formed  first  at  the  periphery  of  the  cell  and  later  in  the  interior  (Figs.  277 


THE   DEVELOPMENT   OF  THE   MUSCULAR   SYSTEM. 


309 


and  278.)    At  the  same  time  they  increase  in  number  by  longitudinal  splitting. 
The  cytoplasm  among  the  fibrils  becomes  the  sarcoplasm. 

After  the  granules  which  first  appear  unite  to  form  the  fibrils,  the  latter 


FIG.  275. — Medial  view  of  a  reconstruction  of  the  muscles  of  the  upper  extremity  of  a  human 
embryo  of  16  mm.  (about  6  weeks).  Lewis. 

The  muscle  arising  on  the  scapula  (at  the  left  of  the  figure)  and  passing  toward  the  right  is  the 
subscapular.  The  small  muscle  just  below  the  subscapular  is  the  teres  major;  below  the 
latter  and  hanging  downward  is  the  latissimus  dorsi.  Note  the  cut  end  of  the  pectoralis 
minor  just  to  the  right  of  the  narrow  portion  of  the  subscapular.  Running  from  this  cut  end 
toward  the  right  is  the  biceps.  The  muscle  at  the  lower  edge  of  the  figure  in  the  arm  region 
is  the  triceps.  In  the  forearm  region,  the  muscle  crossing  the  end  of  the  biceps  is  the  pro- 
nator  teres.  Below  the  pronator  teres,  extending  from  the  elbow  to  the  thumb  region  is  the 
flexor  carpi  radialis.  Below  the  latter  and  extending  to  a  point  opposite  the  thumb,  is  the 
palmaris  longus.  Beneath  the  palmaris  longus  and  dividing  into  branches  which  pass  to  the 
2d,  3d,  4th,  and  5th  digits  is  the  flexor  sublimis  digitorum.  The  muscle  passing  to  the 
thumb  is  the  flexor  longus  pollicis.  .  The  muscle  at  the  lower  border  of  the  figure  in  the  fore- 
arm region  is  the  flexor  carpi  ulnaris. 


FIG.  276. — Myoblasts  in  different  stages  of  development.     Godlewski. 

The  upper  cell  represents  a  myoblast  with  granular  cytoplasm  (from  sheep  embryo  of  13  mm) ;  the 
middle,  a  myoblast  with  fibrils  in  process  of  formation  (from  guinea-pig  embryo  of  10  mm.); 
the  lower,  a  myoblast  with  still  further  differentiated,  segmented  fibrils  (from  a  rabbit 
embryo  of  8.5  mm.). 

are  apparently  quite  homogeneous.     Later  they  become  differentiated  into  two 
distinct  substances  which  alternate  throughout  their  length  and  produce  the 


310 


TEXT-BOOK  OF  EMBRYOLOGY. 


characteristic  cross  striation.  The  nature  of  this  differentiation  is  not  known. 
One  investigator  holds  that  both  substances  are  derived  from  the  original 
granules  that  unite  to  form  the  fibrils,  alternate  granules  being  composed  of  like 
substance  and  united  by  delicate  strands  of  the  other  substance. 

While  the  fibrils  are  being  formed,  the  nuclei  of  the  myoblasts  undergo  rapid 
mitotic  division.  When  the  cells  are  about  filled  with  fibrils,  the  nuclei  migrate 
to  the  periphery  where  they  are  situated  in  the  fully  formed  fiber  (Fig.  278). 
Each  fiber  thus  possesses  a  number  of  nuclei,  whether  it  is  derived  from  one 
myoblast  or  from  several. 


A. 
B 


^^^jjji^^m 

£S28$s  \\^^-^x* , '';/  f  i  I  Uy&Kfi  *\  ;fe^ 

?™f^,^V  <~>'XyXT  J]   I      \    <X/,fc.  .JTyJ 


FIG.  278 

FIG.  277. — From  a  cross  section  of  developing  voluntary  striated  muscle  in  the  leg  of  a  pig  embryo 

of  45  mm.,  showing  fibril  bundles  at  the  periphery  of  the  cells.     MacCallum. 
FIG.  278. — From  a  cross  section  of  developing  voluntary  striated  muscle  in  the  leg  of  a  pig  embryo 

of  75  mm.,  showing  fibril  bundles  more  numerous  than  in  Fig.  277.     A,  Central  vesicular 

nucleus;  B.  peripheral  more  compact  nucleus.     MacCallum. 


For  some  time  at  least,  the  number  of  fibers  in  a  developing  muscle  increases 
by  division  of  those  already  formed.  This  process  would  produce  a  certain 
degree  of  enlargement  of  the  muscle  as  a  whole.  Later  the  increase  in  the 
number  of  fibers  ceases,  and  the  muscle  grows  by  enlargement  of  the  individual 
fibers.  It  is  not  certain  at  what  period  in  development  the  increase  in  the  num- 
ber of  fibers  ceases. 

In  many  muscles  development  is  further  complicated  by  a  retrograde  proc- 
ess—a degeneration  of  some  of  the  fibers.  This  occurs  quite  regularly  in  the 
extremities.  A  well  fibrillated  fiber  first  presents  a  homogeneous  appearance, 
then  becomes  vacuolated,  the  nuclei  disintegrate,  and  finally  the  whole 
structure  disappears.  Mesenchymal  (or  connective)  tissue  takes  its  place,  and 
the  remaining  fibers  are  thus  grouped  into  bundles  and  the  bundles  into 
muscles.  This  would  account  to  a  certain  extent  for  the  intermuscular  con- 


THE  DEVELOPMENT  OF  THE  MUSCULAR  SYSTEM.  311 

nective  tissue,  the  perimysium  and  endomysium,  the  epimysium  being  derived 
from  the  mesenchymal  tissue  which  originally  surrounded  the  muscle. 

THE  VISCERAL  MUSCULATURE. 

The  visceral  musculature  is  derived  wholly  from  the  mesoderm,  but  not 
from  the  myotomes.  The  striated  involuntary  muscle  or  heart  muscle  is  de- 
rived from  the  mesothelial  lining  of  the  ccelom,  the  smooth  muscle  from  the 
mesenchymal  tissue  in  various  regions  of  the  body.  The  heart  muscle  develops 
only  in  connection  with  the  heart  and  consequently  occurs  in  the  adult  only  in 
that  organ.  Smooth  muscle  develops  to  form  integral  parts  of  certain  structures 
such,  for  example,  as  the  alimentary  tube,  glands,  blood  vessels,  and  skin. 

Histogenesis  of  Heart  Muscle. 

When  the  simple  tubular  heart  is  first  formed,  the  splanchnopleure  projects 
into  the  ccelom  (primitive  pericardial  cavity)  along  each  side  (Fig.  194;  also  p. 
222).  The  mesothelium  covering  these  projections  is  destined  to  give  rise  to 


y^7"r;\     / 


FIG.  279. — From  a  section  of  developing  heart  muscle  from  a  rabbit  embryo  of  9  mm.     Godlewski 

a,  Cell  body  with  granules  arranged  in  series;  b,  cell  body  with  centrosome  and  attraction  sphere; 

c,  branching  fibril;  d,  fibrils  extending  through  several  cells. 

the  myocardium.  The  mesothelial  cells  which  are  at  first  closely  packed  to- 
gether with  but  little  intercellular  substance,  assume  irregular  branching  forms 
and  the  branches  anastomose  freely  (Fig.  279).  After  the  cells  become  loosely 
arranged,  they  again  become  closely  packed  to  form  a  compact  syncytium,  in- 
dividual cells  apparently  assuming  the  shape  of  heavy  bands  (Fig.  280).  Ir- 
regular transverse  bands  next  appear,  dividing  the  syncytium  into  the  so-called 


312 


TEXT-BOOK  OF  EMBRYOLOGY. 


heart  muscle  cells.  These  may  or  may  not  represent  the  origina.  cells  or 
myoblasts.  At  all  events  the  muscle  fibrils  are  continuous  across  the  lines. 
The  nuclei  proliferate  in  the  syncytium  but  remain  in  the  central  part  of  the 
bands  or  cells,  instead  of  migrating  to  the  periphery  as  in  striated  voluntary 
muscle. 

While  the  cells  are  still  loosely  arranged,  rows  of  granules  appear  in  the 
cytoplasm,  and  the  granules  in  each  row  unite  to  form  a  fibril  (Fig.  279).     The 

fibrils  are  at  first  confined  to  individual 
cell  areas,  but  as  the  cells  come  closer 
together  to  form  the  compact  syncytium, 
they  extend  through  several  cell  areas 
and  run  in  different  directions  (Fig.  280). 
As  development  proceeds  the  fibrils  be- 
come more  nearly  parallel  (Fig.  281). 
They  are  first  formed  in  the  peripheries 
of  the  cells,  but  later  also  in  the  interior, 
except  in  a  small  area  immediately  sur- 
rounding the  nucleus,  where  a  small 
amount  of  undifferentiated  cytoplasm 
remains.  The  latter  is  continuous 
with  the  cytoplasm  or  sarcoplasm 
among  the  fibrils.  As  in  voluntary 
striated  muscle  the  fibrils  become  differ- 
entiated into  two  distinct  substances 
which  alternate  with  each  other,  thus 
producing  the  transverse  striation. 


FIG.    280. — From   a   section   of    developing 
heart  muscle  in  a  rabbit  embryo  of  9  mm. 
Godlewski. 
The  cells  form  a  compact  syncytium. 


Histogenesis  of  Smooth  Muscle. 

The  mesenchymal  cells  which  are  destined  to  produce  smooth  muscle  cells 
are  not  grouped  into  any  particular  primitive  structures  like  the  mesodermic 
somites.  They  are  simply  scattered  through  the  general  mass  of  mesenchymal 
tissue  and,  like  other  mesenchymal  cells,  possess  irregular  branching  forms  and 
distinct  spherical  nuclei.  The  internal  changes  by  which  these  cells  are  con- 
verted into  muscle  cells  are  not  well  known.  The  contractile  elements — 
the  fibrillae — probably  represent  highly  modified  portions  of  the  original  cyto- 
plasm but  the  manner  in  which  the  cytoplasm  is  transformed  into  fibrillae  has 
not  been  determined.  The  external  changes  consist  essentially  in  an  elonga- 
tion of  the  irregular  mesenchymal  cells.  The  result  of  this  elongation  is  usually 
a  spindle-shaped  cell,  but  exceptionally  cells  forked  at  one  or  both  ends  are 
produced.  The  original  spherical  nucleus  also  shares  in  the  elongation  and 
becomes  rod-shaped. 


THE   DEVELOPMENT   OF  THE   MUSCULAR   SYSTEM.  313 

In  some  cases,  for  example  in  the  muscular  layers  of  the  gastrointestinal 
tract,  distinct  bands  or  sheets  of  smooth  muscle  are  formed  in  which  the  cells 
are  closely  packed  and  lie  approximately  parallel.  In  other  cases,  such  as  the 
mucosa  of  the  intestine  and  the  capsules  of  certain  glands,  the  muscle  cells 
develop  in  little  groups  or  as  isolated  cells. 

Anomalies. 

More  or  less  of  the  muscular  system  is  involved  in  some  of  the  gross  anoma- 
lies or  malformations  of  the  body.  For  example,  congenital  defects  in  the  cen- 
tral nervous  system  (anencephaly,  rachichisis,  etc.)  are  necessarily  accompanied 
by  atrophy  or  faulty  development  of  certain  parts  of  the  muscular  system.  In 
the  case  of  ventral  median  fissure  of  the  abdominal  wall  (gastroschisis),  the 


FIG.  281. — From  a  section  of  developing  heart  muscle  in  a  rabbit  embryo  of  10  mm.     Godleuvski, 
The  fibrils  are  segmented,  indicating  the  beginning  of  the  cross  striation  characteristic  of  heart  muscle. 

abdominal  muscles  are  naturally  involved.  Such  anomalies  in  the  muscles  are, 
however,  secondary  to  the  other  malformations  and  are  not  due  to  primary 
defects  in  the  muscles  themselves. 

Many  of  the  minor  variations  in  the  muscular  system  occur  in  the  same 
form  or  in  similar  forms  in  different  individuals,  thus  indicating  their  relation  to 
a  fundamental  type.  Many  of  these  are  more  or  less  accurate  repetitions  of 
normal  structures  found  in  lower  animals.  Such  variations  are  probably 
rightly  attributed  to  hereditary  influences.  On  the  other  hand,  there  are  varia- 
tions which  cannot  be  referred  to  conditions  found  in  any  of  the  lower  animals. 
These  constitute  a  class  of  variations  which  must  be  accounted  for  upon  some 
other  basis  than  that  of  heredity.  As  pointed  out  in  the  chapter  on  Teratogene- 
sis  (Chap.  XIX),  external  influences  undoubtedly  play  an  important  part  in  the 
production  of  anomalies  and  it  is  probable  that  similar  influences  act  upon  the 
development  of  the  muscular  system. 

The  scope  of  this  book  does  not  permit  a  description,  or  even  mention,  of  the 
great  number  of  variations  in  the  muscles.  A  few  are  described  here  as  ex- 


314  TEXT-BOOK  OF  EMBRYOLOGY. 

amples;  for  others  the  student  is  referred  to  the  more  extensive  text-books  of 
anatomy. 

EXTRINSIC  MUSCLES  OF  THE  UPPER  EXTREMITY. — The  trapezius  is  some- 
times attached  to  less  than  the  normal  number  of  thoracic  vertebras.  Its 
occipital  attachment  may  be  wanting.  Occasionally  the  cervical  and  thoracic 
portions  are  more  or  less  separated  as  in  some  of  the  lower  animals. 

The  latissimus  dorsi  sometimes  arises  from  less  than  the  usual  number  of 
thoracic  vertebras,  and  from  less  than  the  normal  number  of  ribs.  The  iliac 
origin  may  be  wanting. 

The  rhomboidei  vary  in  their  vertebral  and  scapular  attachments. 

The  number  of  the  vertebral  attachments  of  the  levator  scapulae  may  vary. 
A  small  part  of  the  muscle  is  sometimes  attached  to  the  occipital  bone. 

The  pectoralis  major  not  infrequently  varies  in  the  extent  of  its  attachment 
to  the  ribs  and  sternum. 

The  serrati  vary  in  their  attachment  to  the  ribs. 

The  above  mentioned  extrinsic  muscles  of  the  upper  extremity  vary  prin- 
cipally in  their  attachments.  Since  they  all  appear  well  forward  in  the  cervical 
region  in  the  embryo,  and,  along  with  the  extremity,  gradually  migrate  caudally 
before  acquiring  their  final  attachments,  it  is  not  unlikely  that  the  variations  in 
their  attachments  are  due  to  variations  in  the  extent  of  migration. 

This  serves  to  illustrate  a  factor  which  is  probably  important  in  producing 
variations  in  the  attachments  of  many  other  muscles.  As  stated  in  paragraph 
i,  on  page  295,  the  myotomes  frequently  migrate  very  extensively  during 
their  transformation  into  muscles,  before  the  muscles  have  acquired  their  per- 
manent attachment.  Variations  in  the  extent  of  this  migration  would  naturally 
produce  variations  in  the  final  attachments  of  these  muscles. 

Other  factors  related  to  the  changes  in  the  myotomes,  such  as  fusion,  longi- 
tudinal and  tangential  splitting  (paragraphs  2,  3  and  4,  p.  295)  probably  also 
play  a  part  in  the  production  of  variations. 

A  greater  than  normal  degree  of  fusion  between  two  or  more  myotomes 
might  result  in  the  union  of  muscles  which  are  usually  separate;  a  less  than 
normal  degree  of  fusion  might  result  in  the  separation  of  parts  usually  united. 
Variations  in  the  splitting  of  myotomes  might  produce  similar  results. 

At  the  same  time,  however,  heredity  may  be  the  active  factor  in  some  cases 
where  abnormal  fusions  or  separations  between  muscles  or  parts  of  muscles 
produce  results  resembling  conditions  found  in  lower  animals. 

PRACTICAL  SUGGESTIONS. 

A  description  of  the  technic  for  the  study  of  the  primitive  segments  and  their  differ- 
entiation into  myotomes,  sclerotomes  and  cutis  plates  will  be  found  at  the  end  of  the  Chapter 
on  Connective  Tissue  (p.  217).  The  same  animal  and  the  same  technic  may  be  used  for 
the  study  of  the  succeeding  stages  of  development  of  the  myotomes. 


THE   DEVELOPMENT  OF  THE   MUSCULAR  SYSTEM.  315 

The  development  of  the  individual  muscles  from  the  myotomes,  including  the  migration 
of  the  myotomes  and  the  fusion  and  splitting  of  the  myotomes  or  muscles,  is  an  extremely 
difficult  subject  for  practical  study.  Certain  points  can  be  made  out  from  individual  sections, 
but  a  complete  study  is  possible  only  from  serial  sections  of  embryos  in  many  stages  of 
development.  Even  with  serial  sections  it  is  usually  necessary  to  make  wax  reconstructions 
of  the  muscles  in  different  stages  of  development  in  order  to  show  their  relations  to  one 
another  and  to  the  surrounding  structures.  For  methods  of  reconstruction  see  Appendix. 

For  gross  study,  embryos  (human  or  animal)  fixed  and  stained  by  any  ordinary  method 
will  serve.  Possibly  the  best  results  are  obtained  by  fixing  the  embryos  (pig  embryos  are 
usually  easily  procured)  in  Zenker's  'fluid,  cutting  serial  transverse  sections  in  paraffin, 
and  staining  with  Weigert's  hasmatoxylin  and  eosin.  In  sections  treated  by  this  method 
the  developing  muscle  fibers  are  usually  stained  a  more  brilliant  red  than  the  surrounding 
structures. 

For  histogenesis  of  muscle  tissue,  striated  voluntary  or  heart  muscle,  the  following 
technic  yields  good  results.  Fix  small  pieces  of  the  developing  muscle  tissue  (whole 
embryos  if  not  more  than  10-12  mm.  long)  in  Carney's  acetic-alcohol  mixture.  Cut  thin 
sections  in  paraffin,  and  stain  with  Heidenhain's  haematoxylin  (see  Appendix.  A  counter- 
stain  with  eosin  adds  to  the  differentiation.  The  haematoxylin  brings  out  the  anlagen  of  the 
fibrillae. 

Reference  for  Further  Study. 

BARDEEN,  C.  R.:  The  Development  of  the  Musculature  of  the  Body  Wall  in  the  Pig, 
Including  its  Histogenesis  and  its  Relation  to  the  Myotomes  and  to  the  Skeleton  and  to  the 
Nervous  Apparatus.  Johns  Hopkins  Hospital  Reports,  Vol.  XI. 

BARDEEN,  C.  R.,  and  LEWIS,  W.  H.:  Development  of  the  Limbs,  Body  Wall  and  Back 
in  Man.  American  Jour,  of  Anat.,  Vol.  I,  1901. 

BOLK,  L.:  Die  Segmentaldifferenzierung  des  menschlichen  Rumpfes  und  seiner  Extremi- 
taten.  Morph.  Jahrbuch,  Ed.  XXV,  1898. 

FUTAMURA,  R.:  Ueber  die  Entwickelung  der  Facialismuskulatur  des  Menschen. 
Anat.  Hefte,  XXX,  1906. 

GODLEWSKI,  E.:  Die  Entwickelung  des  Skelet-  und  Herzmuskelgewebes  der  Saugetiere. 
Arch.  j.  mik.  Anat.,  Bd.  LX,  1902. 

GRAFENBERG,  E.:  Die  Entwickelung  der  menschlichen  Beckenmuskulatur.  Anat. 
Hejte,  1904. 

HEIDENHAIN,  M.:  Structur  der  contractilen  Materie.  Ergebnisse  der  Anat.  u.  Entwick., 
Bd.  VIII,  1898. 

HEIDENHAIN,  M.:  Ueber  die  Structur  des  menschlichen  Herzmuskels.  Anat.  Anz., 
Bd.  XX,  1901. 

KASTNER,  S.:  Ueber  die  Bildung  von  animalen  Muskelfasern  aus  dem  Urwirbel. 
Arch.  f.  Anat.  u.  Physiol.,  Anat.  Abth.,  Suppl.,  1890. 

KEIBEL,  F.,  and  MALL,  F.  P.:  Manual  of  Human  Embryology,  Vol.  I,  1910. 

KOLLMANN,  J.:  Die  Rumpfsegmente  menschlicher  Embryonen  von  13-35  Urwirbeln. 
Arch.  f.  Anat.  u.  Physiol.,  Anat.  Abth.,  1891. 

LEWIS,  W.  H.:  The  Development  of  the  Arm  in  Man.  American  Jour,  of  Anat.,  Vol.  I, 
1902. 

MAURER,  F. :  Die  Entwickelung  des  Muskelsystems  und  der  elektrischen  Organe.  Also 
Bibliography.  In  Hertwig's  Handbuch  der  vergl.  u.  experiment.  Entwickelungslehre  der 
Wirbeltiere,  Bd.  Ill,  Teil  I,  1904. 


316  TEXT-BOOK  OF  EMBRYOLOGY. 

MACCALLUM,   J.  B.:  On   the    Histology  and  Histogenesis  of    the  Heart -muscle  Cell. 
Anat.  Anz.,  Bd.  XIII,  1897. 

MACCALLUM,  J.  B.:  On  the  Histogenesis  of  the  Striated  Muscle  Fiber  and  the  Growth  of 
the  Human  Sartorius  Muscle.    Johns  Hopkins  Hospital  Bulletin,  Vol.  IX,  1898. 

MALL,  F.  P. :  Development  of  the  Ventral  Abdominal  Walls  in  Man.    Jour.  0}  Mor- 
phology, Vol.  XIV,  1898. 

McGiLL,  CAROLINE:  The  Histogenesis  of  Smooth  Muscle  in  the  Alimentary  Canal  and 
Respiratory  Tract  of  the  Pig.     Internal.  Monatsch.  Anat.  u.  Phys.,  Bd.  XXIV,  1907. 

McMuRRicH,  J.  P.:  The  Phylogeny  of  the  Forearm  Flexors.     American  Jour,  of  Anat., 
Vol.  II,  1903. 

McMuRRicH,  J.  P.:  The  Phylogeny  of  the  Palmar  Musculature.     American  Jour.  0} 
Anat.,  Vol.  II,  1903. 

McMuRRicH,  J.  P.:  The  Phylogeny  of  the  Crural  Flexors.     American  Jour.  0}  Anat., 
Vol.  IV,  1904. 

McMuRRicH,  J.  P.:  The  Phylogeny  of  the  Plantar  Musculature.     American  Jour,  of 
Anat.,  Vol.  VI,  1907. 

POPOWSKY,  I.:  Zur  Entwickelungsgeschichte  der  Dammmuskulatur  beim  Menschen. 
Anat.  Hefte,  1899. 

BUTTON,  J.  B.:  Ligaments,  Their  Nature  and  Morphology.     London,  1897. 

ZIMMERMANN:  Ueber  die  Metamerie  des  Wirbeltierkopfes.     Verhandl.  d.  Anat.  Gesellsch. 
Jena,  1891. 


CHAPTER  XII. 

THE  DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND 
APPENDED  ORGANS. 

The  embryonic  disk,  composed  of  the  three  germ  layers,  primarily  lies  flat 
upon  the  yolk  sac  (see  p.  139;  also  Fig.  82).  A  little  later  the  axial  portion  of 
the  embryo  is  indicated  by  the  primitive  streak,  the  neural  groove  (subsequently 
the  neural  tube),  the  notochord,  and  the  primitive  segments  (Fig.  74).  Then 
along  each  side  of  the  axial  portion  and  at  the  cephalic  and  caudal  ends,  the 


Neural  tube 


_    Yolk  sac 


Hind-gut 


Allantoic  duct 


Belly  stalk 


FIG.  282. — Lateral  view  of  human  embryo  with  14  pairs  of  primitive  segments  (2.5  mm.).     Kollmann. 

The  yolk  sac  has  been  cut  off.     The  fore-gut,  mid-gut  and  hind-gut,  as  indicated  in  the  figure, 

together  constitute  the  primitive  gut.     Compare  with  Fig.  283. 

germ  layers  bend  ventrally  and  medially  and  finally  meet  and  fuse  in  the  mid- 
ventral  line  (p.  141).  The  portion  of  the  entoderm  ventral  to  the  notochord  is 
bent  into  a  tube  which,  for  the  most  part,  becomes  pinched  off  from  the  parent 
entoderm  and  is  suspended  in  the  embryonic  ccelom  by  the  common  mesentery 
(Figs.  141  and  142).  This  entodermal  tube  is  the  primitive  gut.  At  first  it  is 
but  slightly  elongated  and  is  closed  at  both  ends.  On  the  ventral  side,  however, 

317 


318 


TEXT-BOOK  OF  EMBRYOLOGY. 


it  opens  widely  into  the  yolk  sac  (Figs.  282  and  283).  The  primitive  gut,  there- 
fore, has  no  communication  with  the  exterior.  It  communicates  at  its  caudal 
end  with  the  central  canal  of  the  spinal  cord  through  the  neur enteric  canal  (Fig.  84; 
compare  with  85). 

As  development  proceeds,  this  simple  tube  elongates  rapidly  and  becomes 
differentiated  into  distinct  regions.  The  cephalic  end,  in  connection  with  the 
branchial  arches  and  grooves,  becomes  the  dilated  pharyngeal  region.  Caudal 


—  Oral  fossa 

—  Branchial  arch  I 

—  Branchial  arch  II 


Belly  stalk 


FIG.  283. — Ventral  view  of  human  embryo  of  2.4  mm.     His,  Kollmann. 

Note  the  opening  in  the  ventral  wall  of  the  gut.     This  indicates  the  communication  between  the 
gut  and  the  yolk  sac.     The  latter  has  been  removed.     Compare  with  Fig.  282. 

to  and  continuous  with  this,  is  the  short,  narrow  cesophageal  region  which  in 
turn  passes  over  into  the  slightly  dilated  stomach  region.  The  portion  of  the 
gut  caudal  to  the  stomach  is  the  intestinal  region.  During  the  differential 
changes,  the  communication  with  the  yolk  sac  becomes  relatively  smaller,  form- 
ing the  yolk  stalk  which  joins  the  intestinal  portion  a  short  distance  caudal  to  the 
stomach  (Figs.  284  and  285). 

The  Mouth. 

At  a  very  early  period  the  primary  fore-brain  region  bends  ventrally  almost 
at  a  right  angle  to  the  long  axis  of  the  body  to  form  the  naso-frontal  process. 


DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGANS.  -319 

As  the  first  branchial  arch  develops,  it  grows  ventrally  until  it  meets  and  fuses 
with  its  fellow  of  the  opposite  side  in  the  midventral  line,  thus  forming  the 
mandibular  process.  From  the  cephalic  side  of  the  first  arch  a  secondary  proc- 
ess— maxillary  process — develops  and  fills  in  the  space  between  the  arch  itself 
and  the  naso-frontal  process.  These  various  structures  thus  bound  a  distinct 
depression  on  the  ventral  side  of  the  head.  This  depression  is  the  oral  pit,  the 
forerunner  of  the  oral  and  nasal  cavities  (Fig.  283;  compare  with  Figs.  282 
and  122).  The  groove  in  the  midventral  line  between  the  mandibular  processes 
marks  the  symphysis  of  the  lower  jaws.  The  groove  on  each  side  between  the 


Epiglottis 


Tongue 
Hypophysis  — 


Larynx 


Lung 


E.L..X —  Stomach 


Pancreas 


Urachus 


Mesonephric  duct 


Kidney  bud 


FIG.  284  — Alimentary  tube  of  a  human  embryo  of  4.1  mm.     His  Kollmann. 


maxillary  process  and  the  mandibular  process  marks  the  angle  of  the  mouth. 
The  groove  between  the  maxillary  process  and  the  naso-frontal  process  is  the 
naso-optic  furrow,  at  the  dorsal  end  of  which  the  eye  develops. 

The  bottom  of  the  oral  pit  is  formed  by  a  portion  of  the  ventral  body  wall, 
which  separates  the  oral  cavity  from  the  cephalic  end  of  the  gut,  and  which  is 
composed  of  ectoderm  and  entoderm,  with  a  small  amount  of  mesoderm  be- 
tween. This  closing  plate,  the  pharyngeal  membrane,  which  is  still  present  in 
embryos  of  2.15  mm.,  soon  becomes  thinner  and  finally  breaks  away,  leaving 
the  oral  pit  and  the  gut  in  direct  communication  (Fig.  285).  Since  the  oral  pit 
is  lined  with  ectoderm,  the  epithelial  lining  of  the  mouth  or  oral  cavity  is  largely  of 


320 


TEXT-BOOK  OF  EMBRYOLOGY. 


ectodermal  origin.  In  the  medial  line  of  the  roof  of  the  oral  cavity,  near  the 
pharyngeal  membrane,  the  epithelium  (ectoderm)  evaginates  to  form  Rathke's 
pocket.  This  comes  in  contact  with  an  evagination  from  the  floor  of  the  brain 
and  with  it  forms  the  pituitary  body. 

The  further  development  of  the  mouth  consists  of  an  elaboration  of  the 
structures  which  primarily  bound  the  oral  pit  and  the  growth  of  certain  new 
structures  such  as  the  teeth  and  the  tongue.  The  first  branchial  arch  fuses  with 
its  fellow  of  the  opposite  side  in  the  midventral  line  to  form  the  symphysis  of 
the  lower  jaws,  giving  rise  also  to  the  lower  lip  and  chin  region.  As  the  naso- 
frontal  process  continues  to  grow,  two  depressions  appear  on  its  ventral  border, 


Pharynx 


Branchial  arches 
(pharynx) 


Hypophysis    — 


Yolk  sac 

Belly  stalk 
Caudal  gut 


Mesonephros 


Allantoic  duct 


Hind-gut 


Kidney  bud ' 
FIG.  285. — Sagittal  section  of  reconstruction  of  a  human  embryo  of  5  mm.     His,  Kottmann. 

one  on  each  side,  a  short  distance  from  the  medial  line.  These  depressions  are 
the  nasal  pits  which  indicate  the  beginning  of  the  external  openings  of  the  nasal 
passages.  The  part  between  the  nasal  pits  is  destined  to  give  rise  to  the  nasal 
septum  and  the  medial  part  of  the  upper  lip  (Fig.  136).  The  primary  oral 
cavity  is  divided  into  the  oral  cavity  proper  and  the  nasal  cavity  by  outgrowths 
from  the  maxillary  processes.  From  the  medial  side  of  each  maxillary  process 
a  plate-like  structure  grows  across  the  primary  oral  cavity  toward  the  medial 
line  (Fig.  178).  These  two  plates,  or  palatine  processes,  meet  and  fuse  with  the 
lower  part  of  the  nasal  septum  (Fig.  286) .  (For  further  details  of  this  fusion,  see 
page  152  and  page  199).  The  palatine  processes  thus  form  the  palate,  or  the 
roof  of  the  mouth,  which  separates  the  mouth  cavity  from  the  nasal  cavity.  The 
palate  does  not  extend  far  enough  backward,  however,  to  separate  the  posterior 


DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGANS.      321 

part  of  the  nasal  cavity  from  the  pharynx.  Thus  the  posterior  nares  and 
pharynx  are  left  in  communication.  Externally  the  maxillary  processes  extend 
medially,  separate  the  nasal  pits  from  the  oral  cavity,  and  form  the  lateral 
portions  of  the  upper  lip  (Fig.  137). 


""':-\:-\_;f  v^Sr  Nasal  septum 

""]MJ?:^i^ 


J^^;^  Nasal  cavity 

Jacobson's  cartilage 


Palatine  process 


Oral  cavity 

FIG.  286. — From  a  section  through  the  head  of  a  human  embryo  of  28  mm.,  showing  the  nasal 
septum,  the  nasal  cavities,  the  oral  cavity,  and  the  palatine  processes.     Peter. 

The  Tongue.— The  tongue  develops  from  three  separate  anlagen  which 
unite  secondarily.  In  embryos  of  about  3  mm.  a  slight  elevation  appears  on  the 
floor  of  the  pharynx  in  the  region  of  the  first  branchial  arch.  This  is  the 

Tuberculum  impar 


Root  of  tongue 


Inner  branchial 
groove  IV 


Crista  terminalis 


Lung 
FIG.  287. — Floor  of  the  pharyngeal  region  of  a  human  embryo  of  about  3  weeks.     His. 

tuberculum  impar,  being,  as  the  name  indicates,  unpaired,  and  is  destined  to  give 
rise  to  the  tip  and  body  of  the  tongue  (Fig.  287) .  Soon  afterward  two  bilaterally 
symmetrical  elevations  appear  on  the  floor  of  the  pharynx,  which  are  destined  to 
give  rise  to  the  root  of  the  tongue  (Fig.  288) .  These  paired  elevations,  arising 


322  TEXT-BOOK  OF  EMBRYOLOGY. 

in  the  region  of  the  second  and  third  branchial  arches,  gradually  enlarge  and 
unite  with  each  other  and  with  the  tuberculum  impar,  leaving  between  the 
latter  and  themselves,  however,  a  V-shaped  groove  (Fig.  289).  At  the  apex  of 
the  groove  there  is  a  depression — the  foramen  cacum  linguce — which  is  the  ex- 
ternal opening  of  the  thyreoglossal  duct  (see  p.  333).  The  groove  later  disap- 
pears, but  its  position  is  indicated  in  the  adult  by  the  vallate  papillae. 

According  to  Hammar,  the  tuberculum  impar  is  a  transitory  structure  and  does  not 
give  rise  to  the  tip  and  body  of  the  tongue.  The  tip  and  body  are  derived  from  a  much 
more  extensive  elevation  in  the  floor  of  the  pharynx. 

The  tongue  as  a  whole  enlarges  and  grows  from  its  place  of  origin  toward 
the  entrance  to  the  primary  oral  cavity.  For  a  time  it  practically  fills  the  cavity. 
When  the  palate  develops  it  recedes  and  finally  comes  to  lie  on  the  floor  of  the 
oral  cavity  proper,  as  in  the  adult.  The  growth  of  the  tongue  involves  the 


Tuberculum  impar 

Root  of  tongue 
Epiglottis 


FIG.  288. — Floor  of  pharyngeal  region  of  a  human  embryo  of  12.5  mm.     His. 

epithelial  lining  of  the  pharynx  and  oral  cavity  and  also  the  underlying  mesen- 
chymal  tissue.  The  latter  produces  the  connective  tissue  and  at  least  a  part  of 
the  intrinsic  muscle  fibers  of  the  tongue.  The  papillae  involve  the  epithelium 
and  connective  tissue,  while  the  glands  and  taste  buds  are  derived  from  the 
epithelium  alone. 

The  portion  of  the  lingualis  muscle  innervated  by  the  facial  (VII)  nerve  is  probably 
derived  from  the  mesenchymal  tissue  in  the  tongue  anlage.  The  rest  of  the  muscle  is 
innervated  by  fibers  from  the  hypoglossal  (XII)  nerve,  indicating  a  possible  derivation  from 
certain  rudimentary  segments  in  the  occipital  region  which  correspond  to  the  three  roots  of 
the  nerve.  This  would  make  it  appear  that  during  phylogenesis  a  part  of  the  lingualis 
muscle  has  grown  into  the  tongue  from  a  region  caudal  to  the  last  branchial  arch 

The  lingual  papilla  begin  to  develop  during  the  third  month.  Their 
development  is  limited  to  the  dorsum  of  the  tongue  and  to  the  portion  derived 
from  the  tuberculum  impar.  In  other  regions  slight  elevations  may  appear,  but 
not  in  the  form  of  distinct  papillas.  The  fungiform  and  'filiform  papillae  appear 
as  pointed  elevations  in  the  connective  tissue,  which  push  their  way  into  the 
epithelium,  the  latter  at  the  same  time  being  raised  above  the  surface  over  these 


DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGANS.      323 

points.  Gradually  the  little  masses  of  connective  tissue  assume  the  shapes 
characteristic  of  fungiform  or  filiform  papillae.  During  the  fifth  month 
the  epithelium  between  the  papillae  apparently  degenerates  to  some  extent, 
thus  leaving  them  projecting  still  farther  above  the  surface.  The  forma- 
tion of  papillae  probably  goes  on  for  some  time  after  birth,  since  at  birth  their 
form,  size,  number  and  arrangement  are  not  the  same  as  at  later  periods.  It  is 
an  interesting  fact  that  the  filiform  papillae  lose  many  of  their  taste  buds  after 
the  child  is  weaned. 

The  anlage  of  the  vallate  papillae  appears  as  a  ridge  along  the  V-shaped  line 
of  fusion  between  the  paired  and  unpaired  portions  of  the  tongue.  The  ridge  is 
apparently  formed  by  the  ingrowth  of  a  solid  mass  of  epithelium  along  each 
side,  although  the  connective  tissue  between  the  masses  may  grow  toward  the 
surface  to  some  extent.  Later  the  ridge  is  broken  up  into  the  individual  papillae 


Tuberculum  impar 


Root  of  tongue 


FIG.  289. — Dorsal  view  of  the  tongue  of  a  human  embryo  of  20  mm.     His,  Bonnet. 


by  the  ingrowth  of  the  epithelium  at  certain  points.  The  more  superficial  cells 
of  the  masses  then  degenerate,  thus  leaving  each  papilla  surrounded  by  a  trench 
and  wall. 

The  development  of  the  lingual  glands  is  confined  for  the  most  part  to  the 
root  and  inferior  surface  and  to  the  region  of  the  vallate  papillae.  The  glands 
begin  to  develop  during  the  fourth  month  as  solid  ingrowths  of  epithelium,  the 
mucous  glands  appearing  first,  the  serous  somewhat  later.  The  epithelial 
masses  acquire  lumina  and  grow  deeper  into  the  tongue,  where  they  usually 
branch  and  coil  to  form  the  secreting  portions.  The  latter  open  to  the  surface 
through  the  original  ingrowths  which  become  the  ducts.  Ebner's  glands 
develop  from  the  bottoms  of  the  trenches  around  the  vallate  papillae. 

The  Teeth. — The  development  of  the  teeth  involves  the  ectoderm  and 
mesoderm,  the  former  giving  rise  to  the  enamel,  the  latter  to  the  dentine  and 
pulp.  In  human  embryos  of  12-15  mm-  (thirty-four  to  forty  days),  before 
the  lip  groove  is  formed,  a  thickening  of  the  epithelium  (ectoderm)  takes  place 


324 


TEXT-BOOK  OF  EMBRYOLOGY. 


along  the  edges  of  the  processes  that  bound  the  slit-like  entrance  to  the  mouth. 
When  the  lip  groove  appears  (Fig.  178),  the  epithelial  thickening  comes  to  lie 
along  the  edge  of  the  jaw,  or  in  other  words,  along  the  edge  of  the  gums.  It 
then  grows  into  the  mesenchymal  tissue  (mesoderm)  of  the  jaw  obliquely  toward 
the  lingual  surface  to  form  the  dental  shelf.  A  little  later  the  dental  groove 
appears  on  the  edge  of  the  jaw,  along  the  line  where  the  ingrowth  of  epithelium 
took  place. 


JT--  Epithelium  of  mouth  cavity 


Neck  of 
enamel  organ 


Germ  of 
permanent  tooth 


.  Bone  of 
lower  jaw 


Dental  papilla    ..— S-»*j 


FIG.  290. — Section  of  developing  tooth  from  a  35  months  human  fcetus.     Szymonowicz. 

Note  the  portion  of  the  original  dental  shelf  connecting  the  developing  tooth  with  the 

epithelium  of  the  mouth  cavity. 


The  dental  shelf  is  at  first  of  uniform  thickness,  but  in  a  short  time  five 
enlargements  appear  in  it  in  each  upper  and  lower  jaw,  indicating  the  begin- 
nings of  the  milk  teeth.  When  the  embryo  reaches  a  length  of  40  mm.  (an  age  of 
eleven  to  twelve  weeks)  the  mesenchymal  tissue  on  one  side  of  these  enlargements 
(above  and  to  the  inner  side  in  the  upper  jaw,  below  and  to  the  inner  side  in  the 
lower  jaw)  becomes  condensed  and  pushes  its  way  into  the  epithelium.  Each  of 
these  mesenchymal  ingrowths  is  a  dental  papilla.  Thus  at  this  stage  the  anlage 
of  each  tooth  is  a  mass  of  epithelium  fitting  cap-like  over  a  mesenchymal  papilla. 
The  epithelium  is  the  forerunner  of  the  enamel  organ;  the  papilla  is  destined  to 
give  rise  to  the  dentine  and  pulp.  The  anlagen  are  connected  with  one  another 


DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGANS.      325 

by  intermediate  portions  of   the  dental  shelf,  and  with  the  surface  by  the 
original  ingrowth  of  epithelium. 

THE  ENAMEL. — The  epithelial  cells  nearest  the  dental  papilla  become  high 
columnar  in  shape,  forming  a  single  layer.  Those  in  the  interior  of  the  mass 
become  separated  and  changed  into  irregular,  stellate,  anastomosing  cells,  with 
a  fluid  intercellular  substance,  constituting  the  enamel  pulp.  Those  farthest 
from  the  papilla  become  flattened  (Fig.  290;  compare  with  Fig.  291).  Calcifi- 
cation begins  in  the  basal  ends  of  the  columnar  cells,  or  in  the  ends  next  the 


Enamel 

Dentine          |     Enamel  prisms 


Odontoblasts 


Papilla 


Outer 

Inner  . 


Enamel  pulp 


Basal  memb. 


of  enamel 
'  cells 


-      <-     v."^V.     i       •<  '    -•*» 
FIG.  291. — Section  through  the  border  of  a  developing  tooth  of  a  new-born  puppy.     Bonnet. 


papilla,  and  in  the  intercellular  substance,  and  gradually  progresses  throughout 
the  cells,  the  latter  at  the  same  time  becoming  much  more  elongated.  Thus  the 
cells  are  transformed  into  enamel  prisms  which  are  held  together  by  the  calci- 
fied intercellular  substance  (Fig.  291). 

The  formation  of  enamel  begins  in  the  milk  teeth  toward  the  end  of  the 
fourth  month  and  probably  continues  until  the  teeth  break  through  the  gums. 
The  enamel  organ  at  first  surrounds  the  entire  developing  tooth  except  where 
the  papilla  joins  the  underlying  mesenchymal  tissue  (Fig.  290).  Later  the 
deeper  part  of  the  organ  disappears  as  such,  and  the  enamel  is  formed  only  on 
that  part  of  the  tooth  which  eventually  becomes  the  crown.  The  enamel  pulp 
increases  in  amount  for  a  time,  but  subsequently  disappears  as  the  tooth  grows 
into  it  (Fig.  292).  Its  function  is  not  fully  understood.  It  may  serve  as  a  line 


326 


TEXT-BOOK  OF  EMBRYOLOGY. 


of  least  resistance  in  which  the  tooth  grows,  and  it  may  convey  nourishment 
to  the  enamel  cells,  the  enamel  organ  being  non-vascular. 

The  Dentine  and  Pulp. — At  first  the  dental  papilla  is  simply  a  condensation 
of  mesenchyme,  but  later  it  is  converted  into  a  sort  of  connective  tissue  pene- 
trated by  blood  vessels  and  nerves  (Fig.  292).  The  cells  nearest  the  enamel 
organ  become  columnar  and  arranged  in  a  single  layer,  with  the  nuclei 
toward  their  inner  ends.  The  outer  ends  are  blunt,  while  the  inner  ends  are 


Epith.  of  mouth  cavity 


Dental  sac 


Bone  of  jaw 


Blood  vessel 


enamel  cells 


mel 


ntoblasts 


Enamel  pulp 
(remnant) 


Papilla 
FIG.  292. — Longitudinal  section  of  a  developing  tooth  of  a  new-born  puppy.     Bonnet. 


continued  as  slender  processes  that  extend  into  the  pulp  and  probably  fuse 
with  other  cell  processes.  These  columnar  cells  are  the  odontoblasts,  under  the 
influence  of  which  the  lime  salts  of  the  dentine  are  deposited,  and  which  are  com- 
parable with  the  osteoblasts  in  developing  bone. 

Toward  the  end  of  the  fourth  month  the  odontoblasts  form  a  membrane- 
like  structure,  the  membrana  preformativa,  between  themselves  and  the  enamel. 
This  membrane  is  first  converted  into  dentine  by  the  deposition  of  lime  salts, 
after  which  the  process  of  calcification  progresses  from  the  enamel  toward  the 


DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGANS.      327 

pulp.  During  calcification  slender  processes  of  the  odontoblasts  remain  in  minute 
channels,  or  dentinal  canals,  forming  the  dentinal  fibers  which  anastomose  with 
one  another  (Fig.  291).  In  the  peripheral  part  of  the  dentine  certain  areas 
apparently  fail  to  become  calcified  and  form  the  inter  globular  spaces.  The  same 
cells  that  are  originally  differentiated  from  the  mesenchyme  probably  persist 
throughout  development  as  the  odontoblasts  and  produce  the  entire  amount  of 
dentine  in  a  tooth.  Even  in  the  fully  formed  tooth  there  is  a  layer  of  odonto- 
blasts bearing  the  same  relation  to  the  dentine  and  pulp  as  in  the  developing 
tooth.  The  chief  difference  between  dentine  formation  and  bone  formation  is 
that  in  the  latter  the  osteoblasts  become  enclosed  to  form  bone  cells,  while  in 
the  former  the  odontoblasts  merely  leave  processes  enclosed  as  the  cell  bodies 
recede. 

The  pulp  of  the  tooth  is  of  course  derived  from  the  mesenchymal  tissue  in 
the  interior  of  the  dental  papilla  (compare  Figs.  290  and  292).  The  blood 
vessels  and  nerves  grow  in  from  the  underlying  connective  (mesenchymal)  tissue. 

At  an  early  stage  the  mesenchymal  tissue  around  the  anlage  of  the  tooth,  in- 
cluding the  enamel  organ,  condenses  to  form  a  sort  of  sheath,  the  dental  sac, 
which  is  later  ruptured  when  the  tooth  breaks  through  the  gum  (Fig.  292). 
The  cement  is  formed  around  the  root  of  the  tooth  from  the  tissue  of  the  dental 
sac  in  the  same  manner  as  subperiosteal  bone  is  formed  from  osteogenetic  tissue 
(p.  178).  In  fact,  cement  is  true  bone  without  Haversian  systems. 

The  milk  teeth,  which  are  the  first  to  develop  and  the  first  to  appear  above 
the  surface,  are  represented  by  the  medial  incisors,  lateral  incisors,  canines,  and 
molars,  to  the  number  of  ten  in  the  upper  and  ten  in  the  lower  jaw.  They  may 
be  indicated  graphically  thus: 


M. 

C. 

L. 

I. 

M.I.      M 

I. 

L 

.1. 

C. 

M. 

2 

i 

i 

i 

i 

i 

i 

2 

2 

i 

i 

i 

i 

i 

i 

2 

M. 

C. 

L. 

I. 

M 

I.      M 

.1. 

L 

.1. 

C. 

M. 

In  describing  the  formation  of  the  dental  shelf,  it  was  noted  that  the  papillae 
of  the  milk  teeth  grow  into  corresponding  thickenings  of  the  epithelium  (p.  324). 
The  growth  takes  place  from  the  side,  thus  leaving  the  edge  of  the  shelf  free  to 
grow  farther  toward  the  lingual  side  of  the  jaw.  In  this  free  edge  other  tooth 
germs  arise,  which  mark  the  beginnings  of  the  permanent  teeth  (Fig.  290).  In 
addition  to  the  germs  that  correspond  in  position  to  the  milk  teeth,  three  others 
arise  in  each  jaw,  representing  the  true  molars  of  the  adult.  The  latter  arise  in  a 
part  of  the  dental  shelf  which  has  grown  toward  the  articulation  of  the  jaws 
without  coming  in  contact  with  the  surface  epithelium.  The  first  papilla  of 
the  permanent  dentition  to  appear  is  that  of  the  first  molar.  It  appears  im- 
mediately behind  the  second  milk  molar  at  a  time  when  the  milk  teeth  are  well 


328 


TEXT-BOOK  OF  EMBRYOLOGY. 


advanced  (embryos  of  180  mm.,  about  seventeen  weeks).  The  permanent 
incisors  and  canines  appear  about  the  twenty-fourth  week;  the  premolars,  which 
correspond  to  the  milk  molars,  about  the  twenty-ninth  week.  The  second 
molar  does  not  appear  till  after  birth  (six  months),  and  the  third  molar,  or 
wisdom  tooth,  begins  to  develop  about  the  fifth  year. 

The  formation  of  the  anlagen  of  the  permanent  teeth  and  the  development  of 
the  enamel,  dentine  and  pulp  take  place  in  precisely  the  same  manner  as  in  the 
milk  teeth.  The  true  molars  grow  out  through  the  gums  in  the  same  way  as 
the  milk  teeth.  Those  permanent  teeth  which  correspond  in  position  to  milk 
teeth  grow  under  the  latter,  exert  pressure  on  their  roots  and  thus  loosen  and 
finally  replace  them.  The  two  sets  of  teeth  may  be  graphically  represented 
thus: 


Upper 
Upper 

Jaw  —  Permanent, 
Jaw—  Milk, 

M. 
3 

Pm. 

II 
M. 

2 

C. 

II 
C. 

I 

L.I. 

II 
L.I. 

i 

M.I. 

A 

i 

M.  I. 

II 
M.  I. 

i 

L.I. 

L.'l. 

i 

C. 

C. 

i 

Pm. 
M. 

2 

M. 

1! 

3 

Lower 
Lower 

Jaw—  Milk, 
Jaw  —  Permanent, 

3 
M. 

M. 
Pm. 

C. 

II 

C. 

L.I. 

il 
L.I. 

M.I. 

II 
M.I. 

M.I. 
M.I. 

L.I. 

11 
L.I. 

C. 
C. 

M. 

11 
Pm. 

3 

II 
M. 

16 
16 


=  32 


Normally  all  the  epithelium  of  the  dental  shelf,  except  the  parts  directly  con- 
cerned in  the  development  of  the  teeth,  disappears  at  times  which  vary  in  differ- 
ent individuals.  Occasionally,  however,  remnants  of  this  epithelium  give  rise 
to  cystic  structures  (developmental  tooth  tumors). 


Subling.  gland 
Submax.  gland 


Tongue 

-----  Palatine  process 
Submax.  gland 


Lingual  nerve 
FIG.  293. — From  a  transverse  section  through  the  tongue  and  oral  cavity  of  a  mouse  embryo.    Coppert. 

The  Salivary  Glands.* — The  anlage  of  the  submaxillary  gland  appears,  in 
embryos  of  10  to  12  mm.,  as  a  flange  of  epithelium  directed  ventrally  from 
the  portion  of  the  lingual  sulcus  just  caudal  to  the  crossing  of  the  lingual 
nerve.  The  flange  grows  into  the  mesenchyme  of  the  lower  jaw,  and  at  an 
early  period  becomes  triangular  with  its  longest  side  free  and  a  free  vertical 
caudal  border.  Cell  proliferation  begins  at  the  angle  of  union  of  the  two 
borders  and  gradually  progresses  cephalad  along  the  longest  border,  thus 
producing  a  solid  ridge-like  thickening  of  the  latter. 

*The  writers  are  indebted  to  Prof.  H.  von  W.  Schulte  for  a  summary  of  his  as  yet  unpublished 
work  on  the  development  of  the  human  submaxillary  a-d  sublin^ual  glands. 


DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGANS.     329 

The  main  portion  of  the  gland  is  produced  by  a  sprouting  of  the  epithelium 
from  the  angle  of  union  of  the  two  free  borders  of  the  flange  and  grows  deep 
into  the  mesenchyme  along  the  mesial  side  of  the  ramus  of  the  mandible. 
The  sprouts  branch  repeatedly  in  the  course  of  their  development,  thus  laying 
the  foundation  for  the  division  of  the  gland  into  lobes  and  lobules. 

The  distal  end  of  the  duct  of  the  submaxillary  (Wharton's)  is  formed  from 
the  ridge-like  thickening  of  the  free  margin  of  the  flange  through  a  dissolu- 
tion of  the  greater  part  of  the  flange  between  the  lingual  sulcus  and  the 
thickened  margin  itself,  thus  freeing  this  portion  of  the  duct  from  the  sulcus. 
By  a  continuation  of  the  growth  which  produced  the  ridge  along  the  free 
border  of  the  original  flange  an  extension  of  this  same  ridge  is  produced  along 
the  bottom  of  the  lingual  sulcus  forward  toward  the  chin  region.  This  portion 
of  the  ridge  is  progressively  constricted  off  from  the  sulcus  from  behind 
forward,  until  finally  the  attachment  of  the  duct  reaches  its  definitive  position 
at  the  side  of  the  frenulum  linguae. 

The  anlage  of  the  Bartolinian  element  of  the  sublingual  gland  appears  as 
a  smaller,  flange  attached  to  the  lateral  border  of  the  submaxillary  flange  near 
the  crossing  of  the  lingual  nerve  and  prolonged  forward  by  an  interrupted 
crest  along  the  lingual  sulcus.  Its  later  development  is  similar  to  that  of  the 
submaxillary. 

A  small  medial  flange  also  on  the  submaxillary  flange  gives  rise  to  a  sprout 
in  much  the  same  manner  as  the  other  anlagen.  While  the  history  of  this 
anlage  is  not  complete  in  the  human  embryo,  it  probably  gives  rise  to  the 
anterior  lingual  gland  (gland  of  Blandin  and  Nuhn).  The  alveolingual  ele- 
ments arise  from  a  keel  attached  to  the  alveolingual  sulcus  (the  groove 
between  the  floor  of  the  mouth  and  the  alveolar  process  of  the  lower  jaw). 

The  parotid  gland  originates  from  the  buccal  sulcus  in  essentially  the  same 
way  as  the  submaxillary  arises  from  the  lingual  sulcus.  The  anlage  then 
continues  to  grow  through  the  mesenchyme  of  the  cheek  across  the  masseter 
muscle,  the  distal  end  branching  freely  to  form  the  secreting  portion  of  the 
gland.  The  outgrowths  are  at  first  solid,  but  later  become  hollow,  the 
proximal  portion  of  the  original  outgrowth  forming  the  parotid  (Steno's) 
duct,  the  more  distal  portions  forming  the  smaller  ducts  and  terminal  tubules. 

The  histogenetic  changes  in  the  salivary  glands  probably  continue  until  the 
child  takes  solid  food,  when  the  glands  become  of  greater  functional  importance. 
In  the  parotid  gland,  which  is  serous  in  man,  the  original,  undifferentiated 
epithelial  cells  undergo  changes  in  form  and  arrangement  so  that  by  the 
twenty-second  week  the  larger  ducts  are  lined  with  a  two-layered  epithelium, 
the  smaller  ducts  with  a  simple  cuboidal  epithelium,  and  the  terminal  tubules  with 
a  single  layer  of  high  columnar  cells.  The  two-layered  epithelium  in  the  larger 
ducts  persists.  The  ducts  lined  with  the  cuboidal  epithelium  become  the 


330 


TEXT-BOOK  OF  EMBRYOLOGY. 


socalled  intermediate  tubules,  the  cells  changing  to  a  flat  type.  The  high 
columnar  cells  of  the  terminal  tubules  become  the  serous  secreting  cells. 

Quite  similar  changes  also  occur  in  the  submaxillary,  but  in  foetuses  of 
eight  to  nine  months  the  crescents  of  Gianuzzi  appear  as  masses  of  darkly 
staining  cells  forming  the  ends  or  sides  of  the  terminal  tubules.  The  crescents 
at  first  border  on  the  lumina,  but  later,  probably  by  a  process  of  evagination, 
come  to  lie  on  the  surface  of  the  tubules. 

The  beginning  of  the  secretory  function  may  be  detected  by  a  diminution  in 
the  affinity  of  the  cells  for  stains. 

The  Pharynx. 

The  pharynx  develops  from  the  cephalic  end  of  the  primitive  gut.  This 
part  of  the  gut  is  primarily  of  uniform  diameter,  is  broadly  attached  by  meso- 
derm  to  the  dorsal  body  wall,  and  ends  blindly  (Fig.  285).  When  the  branchial 
arches  and  grooves  develoo  in  this  (the  cervical)  region,  they  affect  the  gut  as 


Neural  tube 
(brain) 


Maxillary  process 
Mandibular  process 


Heart 


Notochord 


Branchial  arches  and 
r  grooves  (pharynx) 

L\ 


•/•-  Lung  groove 


FIG.  294. — Sagittal  section  through  the  head  of  a  human  embryo  of  4.2  mm.  (31-34  days).     His. 

well  as  the  periphery  of  the  body.  The  arches  form  ridges  on  the  surface  of  the 
body  (Fig.  122)  and  at  the  same  time  form  ridges  on  the  wall  of  the  gut.  The 
grooves  form  pockets  which  alternate  with  the  arches  (Fig.  294).  The  pockets 
in  the  pharyngeal  cavity,  or  inner  branchial  grooves,  are  directed  outward 
toward  corresponding  outer  branchial  grooves  (Fig.  287).  The  arches  are 
covered  externally  with  ectoderm,  internally  with  entoderm,  and  are  filled  with 
mesoderm.  Between  the  arches,  or  in  the  grooves,  the  ectoderm  and  entoderm 
are  in  contact  or  nearly  so.  Thus  the  pharynx  is  not  surrounded  by  a  ccelomic 
cavity. 


DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGANS.      331 

Since  the  branchial  arches  develop  in  such  a  way  that  they  are  successively 
smaller  from  the  first  to  the  fourth,  the  pharyngeal  cavity  becomes  funnel- 
shaped  (Fig.  294).  It  also  becomes  somewhat  flattened  in  the  dorso- ventral 
direction,  and  in  the  earlier  stages  when  the  arches  and  grooves  are  fully  formed, 
the  pharynx  constitutes  approximately  one-third  the  entire  gut  (Fig.  285). 
Primarily  the  pharyngeal  cavity  is  separated  from  the  oral  cavity  by  the  pharyn- 
geal membrane  (see  p.  319;  also  Fig.  282).  When  this  ruptures  and  disappears 
(during  the  fourth  week  ?)  the  two  cavities  are  in  open  communication.  What 
point  in  the  adult  represents  the  attachment  of  the  pharyngeal  membrane  is 
not  known;  but  the  glosso-  and  pharyngopalatine  arches  (pillars  of  the  fauces) 
are  usually  considered  as  the  boundary  between  the  mouth  and  pharynx.  The 
caudal  limit  of  the  pharynx  is  the  opening  of  the  larynx  (Figs.  285  and  294). 

Thus  in  the  early  stages  the  general  adult  character  of  the  pharynx  is  es- 
tablished. While  the  branchial  arches  and  grooves  undergo  profound  changes, 
the  pharyngeal  cavity  retains  the  same  relation  to  the  mouth  and  to  the  oeso- 
phagus and  respiratory  tract.  The  cavity  becomes  relatively  shorter,  however, 
and  the  alternating  ridges  and  pockets  in  its  walls  are  lost  as  the  arches  and 
grooves  are  transformed  into  other  structures.  The  metamorphosis  of  the 
arches  and  grooves  is  considered  elsewhere  (p.  149). 

THE  TONSILS. — The  tonsils  arise  in  the  region  of  the  ventral  part  of  the 
second  inner  branchial  groove.  During  the  third  month  the  epithelium 
(entoderm)  grows  into  the  underlying  connective  (mesenchymal)  tissue  in  the 
form  of  a  hollow  bud.  From  this,  secondary  buds  develop,  which  are  at  first 
solid,  but  later  (during  the  fourth  or  fifth  month)  become  hollow  by  a  disappear- 
ance of  the  central  cells  and  open  into  the  cavity  of  the  primary  bud,  thus  form- 
ing the  crypts.  Lymphoid  cells  wander  from  the  neighboring  blood  vessels,  or 
are  derived  directly  from  the  epithelium  (Retterer),  and  with  the  connective 
tissue  form  a  diffuse  lymphatic  tissue  under  the  epithelium  (Fig.  295).  By  the 
eighth  month  the  cells  become  more  numerous  in  places,  and  by  the  third 
month  after  birth  form  distinct  lymph  follicles  with  germinal  centers.  The 
formation  of  follicles  goes  on  slowly  and  is  probably  not  complete  until 
some  time  after  birth. 

The  Lingual  Tonsils. — The  lymphatic  tissue  of  the  tongue  develops  in  rela- 
tion to  the  lingual  glands.  During  the  eighth  month  lymphoid  infiltration 
occurs  around  the  ducts  of  the  glands,  and  the  connective  tissue  acquires  the 
reticular  character.  True  follicles  probably  do  not  appear  until  the  child  is  at 
least  five  years  old. 

The  Pharyngeal  Tonsils. — During  the  sixth  month  small  folds  appear  in  the 
mucous  membrane  of  the  roof  of  the  pharynx  and  become  diffusely  infiltrated 
with  lymphoid  cells.  This  occurs  first  in  the  posterior  part  of  the  roof,  but  later 
(seventh  or  eighth  month)  it  extends  forward  and  along  the  sides  of  the  naso- 


332 


TEXT-BOOK  OF  EMBRYOLOGY. 


pharygeal  cavity.  By  the  end  of  foetal  life  the  ridges  become  quite  large. 
Follicles  may  appear  before  birth  or  not  until  one  or  two  years  later.  After 
puberty  the  ridges  almost  completely  disappear,  but  the  adenoid  tissue  remains 
wholly  or  in  part. 

The  bursa  pharyngea  is  an  evagination  from  the  roof  of  the  pharynx  about 
the  upper  border  of  the  superior  constrictor  muscle,  and  is  apparent  in  em- 
bryos of  eleven  weeks.  It  probably  has  no  genetic  relation  to  the  hypophysis. 
Its  significance  is  not  known. 


FIG.  295. — Section  through  the  middle  of  the  developing  tonsil  of  a  human 

embryo  of  5  months.     Stohr. 

6,  Epithelial  buds  (secondary  outgrowths)  from  the  epithelium  lining  the  primary  crypt  (c) ; 
L,  lymphoid  infiltration  of  the  connective  (mesodermal)  tissue. 

THE  BRANCHIAL  EPITHELIAL  BODIES. 

THE  THYREOID  GLAND. — The  thyreoid  arises,  after  the  manner  of  ordinary 
glands,  as  an  evagination  from  the  epithelium  of  the  pharynx.  It  appears  in 
embryos  of  3  to  5  mm.  as  a  ventral  outgrowth  of  epithelium  in  the  floor  of  the 
pharynx,  at  the  point  where  the  tuberculum  impar  and  the  two  paired  anlagen 
of  the  tongue  join  (Fig.  296).  This  point  is  the  foramen  caecum  linguae  which 
has  already  been  mentioned  in  connection  with  the  development  of  the  tongue 
(p.  322).  The  evagination  grows  into  the  mesodermal  tissue  in  the  ventral  wall 
of  the  neck,  and  forms  a  transverse  mass  of  epithelium.  The  latter  breaks  up 
into  irregular  cords  of  cells  which,  by  a  further  process  of  budding,  grow  cau- 
dally  along  the  ventral  surface  of  the  larynx.  The  cords  of  cells  are  from  the 
first  surrounded  by  connective  tissue  and  later  also  become  surrounded  by  net- 
works of  capillaries  (Fig.  297).  They  ultimately  break  up  into  smaller  masses 
which  become  hollow  and  form  the  alveoli.  Colloid  secretion  begins  toward 
the  end  of  foetal  life  or  soon  after  birth. 

As  the  gland  grows  toward  its  final  position  it  becomes  enlarged  laterally  into 
the  two  lateral  lobes,  which  remain  connected  by  the  isthmus  (Fig.  298).  The 
pyramidal  process  represents  either  a  secondary  outgrowth  from  the  isthmus  or 
one  of  the  lobes,  or  a  remnant  of  the  original  connection  with  the  tongue,  that  is, 


DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGANS.   333 


of  the  thyreoglossal  duct.  The  duct  usually  disappears  for  the  most  part,  but 
certain  structures  sometimes  found  in  the  adult  in  the  line  of  the  duct  are 
possibly  remnants  of  it.  They  have  been  variously  named,  according  to  their 
position,  accessory  thyreoid,  suprahyoid,  and  prehyoid  glands  (Fig.  298). 

A  pair  of  structures,  appearing  first  in  embryos  of  8  to  10  mm.,  arise  as 
evaginations  from  the  ventral  ends  of  the  fourth  inner  branchial  grooves.  They 
grow  into  the  mesodermal  tissue  and  then  caudally  along  the  ventro-lateral  side 


Notochord 


Thymus 


Thyreoid 


Jugular  vein 
Vagus  nerve 


Carotid  artery 
'arathyreoid  (epith.  body) 

Thymus  (in.  br.  groove  III) 


Heart 


FlG.  296. — Transverse  section  through  the  region  of  the  3d  branchial  .groove 

of  an  Echidna  embryo.     Maurer. 
i.  =  Pharynx,  below  which  are  the  paired  anlagen  of  the  tongue . 

of  the  larynx,  where  they  come  into  close  relation  with  the  lateral  lobes  of  the 
thyreoid  (Fig.  298).  They  have  been  called  the  lateral  thyreoids,  and  acquire 
the  thyreoid  structure. 

Considerable  confusion  has  arisen  in  regard  to  the  lateral  thyreoids.  The  earlier  investi- 
gators held  that  they  were  derived  from  the  fourth  groove  and  united  with  the  medial  portion, 
which  appeared  at  the  foramen  caecum,  to  become  integral  parts  of  the  thyreoid.  Further 
researches  among  the  lower  Vertebrates  led  others  to  deny  that  the  thyreoid  arose  other 
than  as  a  medial  anlage,  and  that  the  so-called  lateral  thyreoids  in  the  embryo  were  the 
postbranchial  bodies  which  never  assumed  the  thyreoid  structure,  but  atrophied  and  dis- 
appeared. More  recently  it  has  been  thought  that,  although  the  postbranchial  bodies  do 
not  function  in  the  lower  Vertebrates,  they  may  in  the  higher  Mammals  and  man  unite  with 
the  medial  thyreoid  and  secrete  colloid. 

The  parathyreoids  or  epithelial  bodies  also  come  into  close  relation  with  the 
thyreoid.  They  arise  as  paired  evaginations  from  the  cephalic  sides  of  the  third 


334 


TEXT-BOOK  OF  EMBRYOLOGY. 


and  fourth  grooves,  dorsal  to  the  thymus  and  the  lateral  thyreoid  evaginations 
(Figs.  296  and  299).  As  the  thyreoid  grows  caudally  from  its  point  of  origin, 
these  bodies  come  to  lie  close  to  it  or  may  even  become  embedded  in  it  (Fig.  298). 
They  acquire  a  structure  which  resembles  that  of  the  suprarenal  gland  and  not 


Trachea 


Lateral  lobe 


|  Capillaries 
Isthmus 


FIG.  297.— Section  of  the  right  half  of  the  thvreoid  gland  of  a  pig  embryo  of  22.5  mm.     Born. 


Accessory  thyroeids 
(thyreoglossal  duct) 


Carotid  artery 


P.-th. 

Lat.  thyreoid 
(postbr.  body) 


Rignt  subclavian  artery 


Thymus 


Pyramidal  process 

Carotid  artery 
Lateral  thyreoid 
Isthmus 

Lumen  in  thymus 

» 

Left  subclavian  artery 


Arch  of  aorta 

FIG.  298. — Branchial  groove  derivatives  of  a  rabbit  embryo  of  16  mm.    P.-th.,  parathyreoid 
or  epithelial  body.     Verdun,  Bonnet. 

that  of  the  thyreoid.     Their  relation  to  the  latter  organ  seems  to  be  purely 
topographical. 

THE  THYMUS. — The  thymus  appears  in  embryos  of  about  6  mm.  as  an 
entodermal  evagination  from  the  ventral  part  of  the  third  branchial  groove  on 


DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGANS.   335 

each  side  (Fig.  296).  The  outgrowths  are  at  first  hollow  and  communicate  with 
the  pharyngeal  cavity;  later  they  become  solid  and  (in  embryos  of  14  mm.)  lose 
their  connection  with  the  parent  epithelium.  They  elongate  and  grow  caudally 
in  the  mesodermal  tissue  until  (in  embryos  of  16  mm.)  their  caudal  ends  lie 
ventral  to  the  carotid  arteries  (Fig.  298).  In  embryos  of  29  mm.  their  caudal 
ends  rest  upon  the  cephalic  surface  of  the  pericardium,  their  cephalic  ends 
reaching  to  the  isthmus  of  the  thyreoid.  The  two  parts  eventually  fuse  to  a 
considerable  extent,  but  the  gland  as  a  whole  always  consists  of  two  distinct 
lobes. 

The  gland  continues  to  enlarge,  at  the  same  time  becoming  tabulated  by  the 
ingrowth  of  connective  tissue,  until  the  child  is  two  or  three  years  old.  At  this 
time  it  is  situated  in  the  anterior  mediastinum,  usually  in  the  medial  line.  After, 
this  it  begins  to  atrophy  and  becomes  a  mass  of  fibrous  and  fatty  tissue  through 
the  growth  of  the  interlobular  septa  and  their  encroachment  upon  the  lobules. 
The  classical  view  that  the  thymus  begins  to  atrophy  after  the  second  or  third 
year  and  is  quite  degenerated  in  the  adult  has  recently  been  somewhat  offset 


Para  thyreoid 

(epith.  bodies)  }    TV     ^^\  t.-'     "•-»L-*)J}?f-  Thymus 

«T"/^f 

ffy 

Lat.  thyreoid 
(postbr.  body) 

FIG.  299. — Diagram  of  the  branchial  groove  derivatives  in  man.     Verdun. 

by  the  view  that  comparatively  slight  changes  take  place  in  it  until  puberty. 
According  to  the  latter  view,  degeneration  goes  on  after  puberty  at  a  rate  which 
varies  widely  in  different  individuals,  and  the  thymus  may  persist  as  a  functional 
organ  up  to  the  age  of  sixty  years. 

The  his  to  genesis  of  the  thymus  has  been  a  subject  of  much  study  and  con- 
troversy, not  only  in  regard  to  its  origin,  but  also  in  regard  to  its  change  from 
an  epithelial  to  a  lymphoid  structure  and  the  regressive  changes  in  the  latter. 
It  has  almost  certainly  been  proven  to  be  of  entodermal  origin.  It  is  at  first  an 
epithelial  mass  which  later  becomes  broken  up  into  lobules  by  the  ingrowth  of 
connective  tissue.  In  regard  to  the  histological  changes  which  it  undergoes, 
the  older  views  are  in  general  that  a  "pseudomorphosis"  takes  place;  that  is, 
the  epithelial  elements  are  replaced  by  lymphoid  cells  which  wander  in  from 
the  neighboring  blood  vessels,  Hassall's  corpuscles  being  remnants  of  the 
epithelium.  Later  other  investigators  looked  upon  the  changes  as  a  "  transfer- 


336 


TEXT-BOOK  OF  EMBRYOLOGY. 


FIG.  300. — Hassall's  corpuscle  from 
the  thymus  of  a  human  foetus  of 
70  mm.  Hammar. 


mation,"  asserting  that  the  epithelial  cells  were  transformed  into  lymphoid 
cells  in  situ,  and  that  Hassall's  corpuscles  were  remnants  of  epithelium  and 
disintegrating  blood  vessels.  Some  went  even  so  far  as  to  assert  that 

the  thymus  was  the  first  place  of  origin  of 
the  leucocytes.  More  recent  researches 
furnish  very  strong  evidence  that  no  lymph- 
oid cells  are  derived  from  the  epithelial 
cells  (Maximow),  but  that  the  epithelium  is 
transformed  into  the  reticular  tissue  of  the 
thymus,  in  which  the  lymphoid  cells  undergo 
mitotic  division,  Hassall's  corpuscles  possibly 
representing  compressed  parts  of  the  reticu- 
lum  (Hammar)  (Fig.  300). 

THE  GLOMUS  CAROTICUM. — The  early 
formation  of  the  glomus  caroticum  (carotid 
gland)  has  not  been  observed  in  the  human 
embryo.  From  observations  on  lower 
animals  it  has  not  been  made  clear  whether 
it  is  derived  from  the  entoderm  of  a  branchial  groove  or  from  the  adventitia 
of  the  carotid  artery. 

The  (Esophagus  and  Stomach. 

THE  (ESOPHAGUS. — When  the  primitive  gut  becomes  differentiated  into 
distinct  regions  (p.  318),  the  cesophageal  region  forms  a  comparatively  short 
tube,  of  uniform  diameter,  extending  from  the  pharynx  to  the  stomach  (Fig. 
285).  In  embryos  of  about  3  to  4  mm.  the  anlage  of  the  respiratory  system 
arises  from  the  cephalic  end  of  the  tube  (see  p.  362).  The  latter  is  lined  with 
entoderm  and  broadly  attached  to  the  dorsal  body  wall  by  mesoderm  (Fig.  285). 
During  later  stages  it  becomes  relatively  longer  as  the  heart  recedes  into  the 
thorax  (p.  247),  but  maintains  its  uniform  diameter. 

Further  development  produces  no  marked  changes  in  the  relative  position 
of  the  oesophagus.  It  remains  broadly  attached  to  the  dorsal  body  wall 
throughout  the  life  of  the  individual.  In  other  words,  there  is  never  a  distinct 
mesentery.  The  entoderm  gives  rise  to  the  epithelial  lining  and  the  glands,  the 
surrounding  mesoderm  to  the  connective  tissue  and  muscular  coats. 

THE  STOMACH. — The  anlage  of  the  stomach  can  be  recognized  in  embryos 
of  about  5  mm.  as  a  slight  spindle-shaped  enlargement  of  the  primitive  gut  a 
short  distance  cranial  to  the  yolk  stalk  (Fig.  284).  The  dilatation  goes  on  more 
rapidly  on  the  dorsal  than  on  the  ventral  side,  thus  producing  the  greater  and 
lesser  curvature  respectively.  The  greater  curvature  is  attached  to  the  dorsal 
body  wall  by  the  dorsal  mesogastrium  which  is  a  part  of  the  common  mesentery. 


DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGANS.   337 

The  lesser  curvature  is  connected  with  the  ventral  body  wall  by  the  -ventral 
mesogastrium  (Fig.  301). 

In  further  development,  apart  from  histogenesis,  the  greater  curvature 
becomes  much  more  prominent  and  the  organ  as  a  whole  changes  its  position, 
the  latter  process  beginning  in  embryos  of  12  to  14  mm.  The  cephalic  (car- 
diac) end  moves  toward  the  left  side  of  the  body,  the  pyloric  end  toward  the 
right  At  the  same  time  the  stomach  rotates,  the  greater  curvature  turning 


Ventral  mesogastrium  — — 


—  Aorta 


Spleen 

Dorsal  mesogastrium 
~  Cceliac  artery 

Pancreas 


ms Sup.  mesenteric  artery 


Common  mesentery 


SBr-- Inf.  mesenteric  artery 

.-/ 

"'"•  Hind-gut  (rectum) 
FIG.  301. — Gastrointestinal  tract  and  mesenteries  of  a  human  embryo  of  6  weeks.     Toldl. 


Caecum 


caudally  from  its  dorsal  position  and  the  lesser  curvature  cranially  from  its 
ventral  position.  The  result  is  that  the  organ  comes  to  lie  in  an  approximately 
transverse  position  in  the  body,  with  the  cardiac  end  to  the  left,  the  pyloric  end 
to  the  right,  the  greater  curvature  directed  caudally,  and  the  lesser  curvature 
directed  cranially  (compare  Figs.  285  and  301  with  Figs.  314  and  342).* 

*  These  changes  may  be  more  easily  understood  if  the  student  will  hold  a  closed  book  in  the 
sagittal  plane  in  front  of  him,  with  the  back  of  the  book  toward,  and  the  open  edge  away  from  him. 
The  back  represents  the  greater  curvature,  the  open  edge  the  lesser  curvature.  The  upper  end  of 
the  book  represents  the  cardiac  end  of  the  stomach,  the  lower  end  the  pylorus.  Turn  the  upper 
(cardiac)  end  to  the  left,  the  lower  (pyloric)  end  to  the  right,  at  the  same  time  allowing  the  back  of 
the  book  (the  greater  curvature)  to  drop  downward  on  the  side  toward  the  body.  The  changes  in 
the  position  of  the  book  represent  the  changes  in  the  position  of  the  developing  stomach. 


TEXT-BOOK  OF  EMBRYOLOGY. 

It  is  obvious  that  the  lower  end  of  the  oesophagus  is  carried  toward  the  left 
side  of  the  body  with  the  cardiac  end  of  the  stomach,  and  at  the  same  time 
twisted  so  that  the  side  which  originally  faced  the  left  conies  to  face  ventrally. 
The  changes  in  the  mesentery  which  accompany  the  changes  in  the  stomach 
are  described  elsewhere  (p.  380). 

The  torsion  of  the  stomach' also  produces  an  asymmetrical  condition  of  the 
vagi  nerves.  The  latter  reach  the  stomach  before  it  changes  its  position.  As 
the  changes  take  place,  the  left  nerve  is  carried  around  to  the  left  and  ventrally 
so  that  in  the  adult  it  passes  through  the  diaphragm  ventral  to  the  oesophagus 
and  extends  over  the  ventral  surface  of  the  stomach.  The  right  nerve  passes 
over  the  dorsal  surface  of  the  stomach. 

The  Intestine. 

When  the  primitive  gut  is  differentiated  into  recognizable  regions  (p.  318) 
the  intestinal  region  forms  a  simple  tube,  of  uniform  diameter,  extending  from 
the  stomach  to  the  caudal  end  of  the  embryo  where  it  ends  blindly.  The  yolk 
stalk  is  attached  to  the  intestine  a  short  distance  from  the  stomach.  Near  the 
caudal  end  the  allantoic  duct  arises  (p.  118).  The  lumen  of  the  yolk  stalk  and 
of  the  allantoic  duct  is  continuous  with  that  of  the  intestine  (Fig.  285).  In 
embryos  of  2  to  3  mm.  the  liver  anlage  arises  from  the  ventral  side  of  the 
intestine  near  the  stomach,  that  is,  from  that  part  of  the  intestine  which  is  to 
become  the  duodenum.  In  embryos  of  3  to  4  mm.  the  pancreas  anlage  arises 
in  the  same  region,  in  part  from  the  liver  evagination  and  in  part  from  the  dorsal 
side  of  the  intestine  (Fig.  285). 

The  intestine  as  a  whole  is  suspended  in  the  abdominal  cavity  by  the'dorsal 
mesentery  which  is  attached  to  the  dorsal  body  wall  and  which  is  continuous 
with  the  dorsal  mesogastrium.  A  ventral  mesentery,  continuous  with  the 
ventral  mesogastrium,  is  present  only  at  the  cephalic  end  of  the  duodenum 
(Fig.  301). 

The  further  development  of  the  intestine,  apart  from  histogenesis,  consists 
very  largely  of  the  formation  of  loops  and  coils,  due  to  an  enormous  increase  in 
the  length  of  the  tube.  The  abdominal  cavity  at  the  same  time  enlarges  to 
accommodate  the  increased  bulk.  As  the  stomach  changes  its  position  (p.  337), 
the  duodenum  comes  to  lie  obliquely  across  the  body  and  forms  a  curve  with  the 
concavity  directed  dorsally  (Fig.  301).  The  rest  of  the  intestine  forms  a  loop 
which  extends  ventrally  and  caudally  as  far  as  the  umbilicus.  The  arms  of  the 
loop  are  almost  parallel  and  the  cephalic  arm  lies  a  little  to  the  left  of  the  caudal. 
The  apex  of  the  loop  extends  into  the  umbilical  ccelom  and  is  attached  to  the  yolk 
stalk.  From  the  dorsal  end  of  the  caudal  arm  the  intestine  extends  directly 
to  the  caudal  end  of  the  body  (Fig.  301). 

Soon  after  the  loop  is  formed  a  small  evagination  appears  on  its  caudal  arm, 
not  far  from  the  apex.  This  is  the  anlage  of  the  cacum  and  marks  the  bound- 


DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGANS.   339 

ary  between  the  small  and  large  intestine  (Fig.  301).  At  this  stage,  therefore, 
all  the  great  divisions  of  the  intestinal  tract  are  distinguishable,  viz. :  the  duodenum 
with  the  ducts  of  the  liver  and  pancreas;  the  mesenterial  small  intestine  with  the 
yolk  stalk;  and  the  colon  extending  from  the  caecum  to  the  caudal  end.  There 
are,  however,  practically  no  differences  between  the  regions,  either  in  structure 
or  in  size. 

In  further  development  the  duodenum  comes  to  lie  more  nearly  transversely 
across  the  body,  thus  assuming  its  adult  position.  Its  mesentery  fuses  with  the 
peritoneum  of  the  dorsal  body  wall  and  the  duodenum  thus  becomes  a  fixed 
portion  of  the  intestinal  tract  (p.  382;  also  Fig.  339).  It  enlarges  a  little  more 


FIG.  302. — Reconstruction  of  the  liver  and  intestine  of  a  human  embryo  of  17  mm.     Mall. 

G.B.,   gall   bladder;  H.  V.,  hepatic   vein;  U.  V.,  umbilical  vein;   1-6,  primary  bends  in  the  long 

intestinal  loop;   i  represents  the  duodenum. 


rapidly  than  the  rest  of  the  small  intestine  and  acquires  a  greater  diameter.  In 
embryos  of  12  to  13  mm.  the  lumen  becomes  obliterated  by  an  overgrowth  of  the 
mucous  membrane  caudal  to  the  ducts  of  the  liver  and  pancreas.  In  embryos 
of  about  15  mm.,  however,  the  lumen  reappears.  It  seems  difficult  to  find  a 
cause  for  this  peculiar  growth  of  the  mucosa. 

Very  shortly  after  the  formation  of  the  long  loop  in  the  intestine,  six  bends 
become  recognizable  in  the  portion  between  the  stomach  and  the  apex  of  the 
loop  (Fig.  302) .  These  bends  later  form  distinct  loops  which  are  destined  to 
become  definite  parts  of  the  small  intestine.  The  first  loop  is  the  duodenum, 
the  development  of  which  has  already  been  considered,  and  which  maintains 
practically  its  original  position.  The  other  five  loops  continue  to  elongate  and 
form  secondary  loops,  all  of  which  push  their  way  into  the  umbilical  coelom 


340 


TEXT-BOOK  OF  EMBRYOLOGY. 


where  they  remain  until  the  embryo  reaches  a  length  of  40  mm.  (compare  Figs. 
303  and  304) .  Then  they  return  very  quickly  to  the  abdominal  cavity  proper. 

After  their  return,  the  primary  loops,  with  the  secondary  loops  derived  from 
them,  come  to  occupy  fairly  constant  positions.  The  second  and  third  move 
to  the  left  upper  part  of  the  abdominal  cavity;  the  fourth  crosses  the  medial 
line  and  occupies  the  right  upper  part.  The  fifth  crosses  back  and  lies  in  the 
left  iliac  fossa;  the  sixth  lies  in  the  pelvis  and  lower  part  of  the  abdominal 
cavity  (Fig.  305). 

Certain  variations  may  occur  but  are  usually  not  considered  as  abnormal. 
The  most  frequent  variation  is  one  in  which  the  fourth  coil,  along  with  the 


FIG.  303. — Reconstruction  of  the  stomach  and  intestine  of  a  human  embryo  of  28  mm.     Mall. 

The  numbers  are  placed  on  the  coils  derived  from  the  primary  bends  as  shown  in 

Fig.  302;  i  represents  the  duodenum. 

second  and  third,  lies  on  the  left  side,  its  usual  position  on  the  right  being  oc- 
cupied by  the  ascending  colon.  Not  uncommonly  the  positions  of  the  fourth 
and  the  second  and  third  are  reversed.  Less  commonly  extra  loops  are  formed. 

Usually  the  proximal  part  of  the  yolk  stalk  disappears  during  fcetal  life.  In 
a  few  cases,  however,  it  persists  as  a  blind  sac  of  variable  length,  known  as 
Meckel's  diverticulum  (see  also  p.  117). 

Even  before  the  loops  return  to  the  abdominal  cavity  the  colon  or  large 
intestine  increases  in  diameter  more  rapidly  than  the  small  intestine.  After 
the  return,  the  caecum  is  carried  across  to  the  right  side  and  comes  to  lie  just 
caudal  to  the  liver.  From  the  caecum  the  colon  extends  across  the  abdominal 


DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGANS.      341 

cavity,  ventral  to  the  duodenum,  forming  the  transverse  colon.  It  then  de- 
scends on  the  left  side  as  the  descending  colon  which  passes  over  into  the  sigmoid 
colon  (Fig.  337).  The  transverse,  the  descending  and  the  sigmoid  portions  of 
the  colon  are  recognizable  in  the  third  month.  Up  to  the  time  of  birth  the 
sigmoid  portion  is  disproportionately  long;  after  birth  the  other  portions 


FIG.  304. — Drawing  from  a  reconstruction  of  a  human  embryo  of  24  mm.     Mall. 
The  intestinal  coils  lie  for  the  most  part  in  the  umbilical  coelom.     C,  caecum;  K,  kidney;  L,  liver. 
S,  stomach;  S.  C.,  suprarenal  gland;  W,  mesonephros;  12,  twelfth  thoracic  nerve;  5,  fifth 
lumbar  nerve. 

grow  relatively  faster.  After  the  fourth  month  the  portion  to  which  the  caecum 
is  attached  grows  downward  in  the  right  side  of  the  abdominal  cavity,  thus  form- 
ing the  ascending  colon  (Fig.  342). 

The  caecum,  which  appears  in  very  early  stages  as  an  evagination  at  the 
junction  of  the  small  and  large  intestines,  for  a  time  continues  to  increase  uni- 
formly in  size.  Then  the  proximal  end  increases  more  rapidly  than  the  distal, 
and  forms  the  caecum  of  adult  anatomy.  The  distal  end,  failing  to  keep  pace 


342  TEXT-BOOK  OF  EMBRYOLOGY. 

in  development,   remains  more   slender  and  forms  the  -vermiform  appendix 
(Fig.  305). 

As  has  already  been  mentioned,  the  primitive  gut  ends  blindly  in  the  caudal 
end  of  the  embryo  (Fig.  284).  The  anal  opening  is  a  secondary  formation. 
On  the  ventral  side  of  the  caudal  end  of  the  body  there  is  formed  a  depression 
known  as  the  anal  pit.  The  mesoderm  at  the  bottom  of  the  pit  becomes  thin- 
ner until  the  ectoderm  comes  in  contact  with  the  entoderm  on  the  ventral  side 
of  the  gut,  thus  forming  the  anal  membrane.  The  area  of  contact  is  not  at  the 


FIG.  305. — Drawing  from  a  model  of  the  small  intestine  in  the  adult.     Ventral  view.     Matt. 

The  intestinal  coils  are  shown  in  the  usual  relative  position.     The  numbers  indicate  the  coils  derived 

from  the  primary  bends  in  the  fcetus  as  shown  in  Figs.  302  and  303. 

extreme  end  of  the  gut,  but  a  short  distance  toward  the  allantoic  duct.  In  the 
meantime,  the  urogenital  ducts  come  to  open  into  that  portion  of  the  gut  which 
lies  just  cranial  to  the  anal  membrane.  The  gut  enlarges  in  this  region  to 
form  the  cloaca.  The  latter  becomes  separated  by  the  urorectal  fold  into  a 
dorsal  portion,  the  rectum,  and  a  ventral  portion,  the  urogenital  sinus  (Figs.  361 
and  363).  At  about  the  time  of  separation  (embryos  of  about  14  mm.  or 
thirty-six  to  thirty-eight  days)  the  anal  membrane  ruptures  and  the  anal  open- 


DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGANS.      343 


ing  is  formed.     The  portion  of  the  gut  caudal  to  the  anus,  known  as  the  caudal 
gut,  normally  disappears. 

Histogenesis  of  the  Gastrointestinal  Tract. 

The  wall  of  the  primitive  gut  is  composed  of  two  layers  —  the  entoderm  which 
lines  the  lumen,  and  the  splanchnic  mesoderm  which  borders  on  the  ccelom  or  body 
cavity.  While  the  germ  layers  are  still  flat,  the  entoderm  is  a  single  layer  of  flat 
cells  with  bulging  nuclei,  but  after  the  closure  of  the  gut  the  cells  become  col- 
umnar. The  splanchnic  mesoderm  is  composed  of  two  layers  —  the  mesothe- 
lium  bordering  on  the  ccelom,  the  cells  of  which  gradually  change  from  flat 


Mesentery 


Mesothelium 


Long. 


Trans. 


muscle 


Epithelium  —  * 


Stroma 


FIG.  306. — Transverse  section  of  the  small  intestine  of  a  pig  embryo  of  32  mm.     Bonnet. 

to  rather  high,  and  a  number  of  indifferent,  branching  mesenchymal  cells 
lying  between  the  mesothelium  and  entoderm.  The  entoderm  is  destined  to 
give  rise  to  the  general  epithelial  lining  of  the  gastrointestinal  tract  and  to  all 
the  glands  connected  with  it.  The  mesothelium  around  the  gut  forms  a  part  of 
the  general  mesothelial  lining  of  the  ccelom,  its  cells  apparently  changing  back 
to  a  flat  type.  The  mesenchymal  tissue  is  destined  to  give  rise  to  all  the  con- 
nective tissue  and  smooth  muscle  of  the  tract.  The  circular  layer  of  muscle 
appears  first,  the  longitudinal  next,  both  appearing  during  the  third  and  fourth 
months,  and  last  of  all  the  muscularis  mucosae  (Fig.  306). 

THE  Mucous  MEMBRANE. — The  mucous  membrane  is  formed  by  the 
epithelium  (entoderm)  and  the  subjacent  mesenchymal  tissue.     In  its  develop- 


344  TEXT-BOOK  OF  EMBRYOLOGY. 

ment  there  are  two  factors  to  be  considered :  (i)  The  formation  of  folds  to  in- 
crease the  absorbing  surface  and  (2)  the  formation  of  secreting  organs  or  glands. 
As  to  the  relation  between  these  two  factors  there  is  a  difference  of  opinion. 
Some  hold  that  both  kinds  of  structures  are  the  result  of  the  same  formative 
process,  that  is,  that  the  glands  are  simply  the  depressions  or  pits  formed  by  the 
intersection  of  folds  at  various  angles,  and  that  the  folds  are  produced  primarily 
by  the  growth  of  the  epithelium  and  mesenchymal  tissue  into  the  lumen  of  the 
gut.  Others  maintain  that  although  the  folds  may  be  produced  by  the  growth 
of  the  epithelium  and  mesenchymal  tissue  into  the  lumen,  the  glands  arise  as 
independent  growths  of  the  epithelium  into  the  subjacent  tissue.  The  latter 

view  is  supported  by  the  fact  that  in 
some  Amphibia  the  glands  appear  before 
the  folds  (Fig.  307).  Recent  work  on 
Mammals  also  favors  this  view. 


i-i  •  A"~  Subm. 

•  :\  The   development  of  the  folds  and 

:-  glands  begins  in  the  different  parts  of  the 
gastrointestinal  tract  at  different  times. 
It  begins  first  in  the  stomach,  then  in  the 

FIG.  307. — Section  through  the  wall  of  the        ,        ,  .          .        .  .     . 

stomach  of  a  frog  embryo.    Ep.,  Epi-     duodenum,  then  m  the  colon,  and  then 

thelium,  with  glands;  S«6m.  submucosa;      jn    the    jejunum    whence     it     progresses 

Muse.,  muscle  layer.     Ratner.  J   J 

slowly  into  the  ileum.  In  the  stomach 

it  is  uncertain  whether  the  crypts  and  glands  are  depressions  left  among 
projections  of  the  mucous  membrane,  or  the  glands  represent  evaginations  of 
the  epithelium  into  the  underlying  tissue.  In  the  case  of  the  large  intestine 
the  same  uncertainty  exists.  If  the  so-called  glands  are  depressions  among 
villous  projections  that  grow  into  the  lumen  of  the  intestine,  they  are  not  true 
glands  from  an  embryological  point  of  view. 

Studies  of  the  development  of  the  mlli  in  the  human  small  intestine  have  led 
to  the  conclusion  that  they  are  formed  primarily  as  growths  of  the  mucosa  into 
the  lumen.  In  embryos  of  19  mm.  the  mucosa  of  the  cephalic  end  is  thrown 
into  a  number  of  longitudinal  folds  (Fig.  308).  These  then  develop  pro- 
gressively toward  the  caudal  end.  Beginning  in  embryos  of  50  to  60  mm.  the 
longitudinal  folds  become  broken  transversely  into  conical  structures,  the 
villi.  The  intestinal  crypts  (of  Lieberkiihn)  possibly  represent  outgrowths  of 
the  epithelium  from  the  bottoms  of  the  intervillous  spaces.  The  duodenal 
(Brunner's)  glands  are  possibly  to  be  considered  as  a  continuation  of  the  pyloric 
glands  of  the  stomach.  They  apparently  grow  as  evaginations  from  the 
intervillous  crypts. 

The  epithelial  lining  of  the  gastrointestinal  tract  is  from  the  beginning  a 
single  layer  of  cells,  although  the  individual  cells  are  altered  in  shape  and 
structure  and  acquire  different  functions  in  different  regions.  There  is  still 


DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGANS.   345 

some  dispute  as  to  whether  the  mucous  cells  are  continuously  being  derived 
from  the  other  epithelial  cells  or,  when  once  formed,  reproduce  themselves  by 
mitosis.  As  a  matter  of  fact,  mitosis  has  been  observed  in  the  mucous  cells  of 
the  stomach. 


FIG.  308. — From  a  reconstruction  of  the  small  intestine  of  a  human  embryo  of  28  mm.,  showing  the 
longitudinal  ridges  which  eventually  become  broken  transversely  to  form  the  villi.     Berry. 

THE  LYMPH  FOLLICLES. — In  the  development  of  the  lymph  follicles  in  the 
gastrointestinal  tract  the  same  question  arises  as  in  the  case  of  the  tonsils  and 
thymus.  Are  the  lymphoid  cells  of  mesodermal  or  of  entodermal  (epithelial) 


FIG.  309. — Sections  through  the  wall  of  the  csecum  of  (a)  a  rabbit  2\  days  and  (b)  5  days  after 
birth,  showing  the  development  of  the  lymph  follicles.  /.  Lymphoid  infiltration  in  the  stroma; 
r,  wandering  cells  in  the  epithelium;  z,  lymphoid  cells  in  the  core  of  a  villus.  Stohr. 

origin?  Evidence  at  present  favors  the  mesodermal  origin.  In  the  case  of 
Peyer's  patches,  collections  of  lymphoid  cells  appear  near  the  blood  vessels  in 
the  stroma  and  neighboring  parts  of  the  submucosa.  These  increase  in  extent, 


346 


TEXT-BOOK  OF  EMBRYOLOGY. 


the  lymphoid  cells  dividing  actively,  and  grow  into  the  bases  of  some  of  the 
villi  and  deeper  into  the  submucosa  (Fig.  309).  Germinal  centers  appear  in 
many  of  the  follicles,  and  the  surrounding  stroma  becomes  densely  infiltrated 
with  the  lymphoid  cells.  Individual  follicles  may  develop,  in  the  manner 
described,  in  any  part  of  the  gastrointestinal  tract.  The  appendix  especially  is 
the  seat  of  extensive  lymphatic  tissue  formation.  It  is  stated  in  the  section  on 
the  lymphatic  system  that  lymph  glands  may  arise  at  any  time  in  any  region  as 
the  result  of  unusual  conditions  (p.  282),  and  this  also  holds  true  in  the  case  of 
lymph  follicles  in  the  digestive  tract. 

The  Development  of  the  Liver. 

The  liver  is  the  first  gland  of  the  digestive  tract  to  appear.  In  embryos  of 
about  3  mm.  a  longitudinal  ridge-like  evagination  develops  from  the  entoderm 
on  the  ventral  side  of  the  gut  a  short  distance  caudal  to  the  stomach,  that  is,  in 


Myotome 

Aorta 

Post,  cardinal  vein 


Upper  limb  bud 
Dorsal  mesentery 

Duodenum 
Liver 


Coelom 

Omphalomesenteric  vein 
Umbilical  vein 

Heart 


FIG.  310. — Transverse  section  of  a  human  embryo  of  5  mm.,  showing  the  liver  evagination  and  the 
breaking  up  of  the  omphalomesenteric  veins  by  the  hepatic  cylinders.     Photograph. 

the  duodenal  portion  of  the  gut  (Figs.  285,  310,  311).  The  cephalic  part  of  the 
evagination  is  solid  and,  being  destined  to  give  rise  to  the  liver  proper,  is  called  the 
pars  hepatica.  The  caudal  part  is  hollow,  its  cavity  being  continuous  with  the 
lumen  of  the  gut,  and  is  destined  to  give  rise  to  the  gall  bladder,  whence  it  is 
called  the  pars  cystica.  Beginning  at  both  the  cephalic  and  caudal  ends,  the 
evagination  as  a  whole  becomes  constricted  from  the  gut  until  (in  embryos  of 
about  8  mm.)  its  only  connection  with  the  latter  is  a  narrow  cord  of  cells  which 


DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGANS.      347 

is  the  anlage  of  the  ductus  chokdochus.  The  pars  hepatica  by  this  time  has 
enlarged  considerably  and  remains  attached  to  the  ductus  choledochus  by  a 
short  cord  of  cells,  the  anlage  of  the  hepatic  duct.  The  pars  cystica  has  also 
become  larger,  its  distal  portion  being  somewhat  dilated,  and  is  connected  with 
the  ductus  choledochus  by  the  anlage  of  the  cystic  duct  (Figs.  312  and  313). 
The  pars  cystica  grows  into  the  ventral  mesentery  and  thus  becomes  sur- 
rounded by  mesodermal  tissue.  The  proximal  portion  continues  to  elongate  to 
form  the  cystic  duct  and  the  distal  portion  becomes  larger  and  more  dilated  to 
form  the  gall  bladder. 


Du. 


V.  pan. 


D.ch. 


H.du. 


G.bl 


FIG.  311. — From    a  model  of  the  duodenum  and  the  primary  evaginations  of  the 

liver  and  pancreas  in  a  5  mm.  sheep  embryo.     Stoss. 

D.pan.,  Dorsal  pancreas;  Du..  duodenum;  D.  ch.,  ductus  choledochus;  G.  bl.,  gall 
bladder;  H .  du.,  hepatic  duct. 

The  pars  hepatica,  or  anlage  of  the  liver  proper,  also  grows  into  the  ventral 
mesentery,  thus  becoming  surrounded  by  mesodermal  tissue.  As  stated  in 
connection  with  the  development  of  the  diaphragm,  the  portion  of  the  mesen- 
tery into  which  the  liver  grows  is  involved  in  the  formation  of  the  septum 
transversum  (p.  376).  Thus  the  developing  liver  becomes  enclosed  in  the 
septum  (Fig.  330) .  The  mesodermal  tissue  gives  rise  to  the  fibrous  capsule  of 
Glisson  and  to  the  small  amount  of  connective  tissue  within  the  gland. 

Although  the  liver  develops  as  a  series  of  outgrowths  from  the  original 
evagination,  there  are  certain  features  in  its  development  which  distinguish  it 
from  glands  in  general.  The  outgrowths  come  in  contact  with  the  omphalomes- 
enteric  veins  which  are  situated  in  the  ventral  mesentery  (p.  263).  They  push 
their  way  into  and  through  the  veins,  breaking  them  up  into  smaller  channels 
(Fig.  310).  They  anastomose  freely  with  one  another,  and  the  veins  send  off 


348 


TEXT-BOOK  OF  EMBRYOLOGY. 


branches  which  circumvent  them.  Thus  there  is  formed  a  network  of  trabec- 
ulae  of  liver  cells,  called  hepatic  cylinders,  the  meshes  of  which  are  filled  with  blood 
vessels.  Therefore  the  liver  is  distinguished  from  other  glands  in  general  in 


Stomach 


Left  hep 
duct 


Gall     _J 
bladder 


Duodenum 


FiG.  312. — From  a  reconstruction  of  the  anlagen  of  the  liver  and  pancreas  and  a  part  of  the 
stomach  and  duodenum  of  a  human  embryo  of  4  weeks.     Felix. 

that  the  hepatic  cylinders,  which  are  comparable  with  the  smaller  ducts  and 
terminal  tubules  of  other  glands,  anastomose,  and  in  that  the  blood  vessels  are 
broken  up  by  the  growth  of  these  cylinders. 


D.V. 


D.F. 


Du. 


FIG.  313.— From  a  reconstruction  of  the  anlagen  of  the  liver  and  pancreas  and  the  stomach 

of  a  human  embryo  of  8  mm.     Hammar. 

D.P,  Dorsal   pancreas:    Du.,  duodenum;    D.V.,  ductus   venosus;    G.B.,  gall   bladder; 
R.I.,  right  lobe  of  liver;  S.,  stomach;   V.  P.,  ventral  pancreas. 

This  mode  of  development  establishes  what  is  known  as  a  sinusoidal  circulation,  which 
differs  from  the  ordinary  capillary  circulation.  The  sinusoids  are  produced  by  the  growth 
of  the  trabecute  of  the  developing  organ  into  large  vessels  and  the  breaking  up  of  the  latter 


DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGANS.   349 

into  smaller  vessels.  It  is  obvious  that  a  sinusoidal  circulation  is  purely  venous  or  purely 
arterial.  Furthermore,  development  of  this  nature  leaves  comparatively  little  connective 
tissue  within  the  gland,  another  feature  characteristic  of  the  liver. 

All  the  blood  carried  to  the  liver  by  the  omphalomesenteric  veins  must 
follow  the  tortuous  course  of  the  sinusoids  before  being  collected  again  and 
passed  on  to  the  heart.  When  the  umbilical  veins  come  into  connection  with 
the  liver  they  also  join  in  the  sinusoidal  circulation.  Subsequently,  however,  a 
more  direct  channel— the  ductus  venosus — is  established  and  persists  for  a 


Aorta 

Inf.  vena  cava 
Coelom 


Ductus 
choledochus 


Right  side 


Suprarenal  glands 


Mesonephros 


Dorsal  mesogastrium 
(greater  omentum) 

Stomach 

Ventral  mesogastrium 
(lesser  omentum) 


Liver 


Left  side 


FlG.  314. — Tran verse  section  of  a  14  mm.  pig  embryo,  through  the  region  of  the  stomach. 
Photograph.     The  arrow  points  into  the  bursa  omentalis. 

short  time.  This  is  probably  due  to  the  large  volume  of  blood  brought  in  by 
the  umbilical  veins.  Finally  the  ductus  venosus  disappears  and  the  sinusoidal 
circulation  remains  as  the  permanent  form.  (For  the  development  of  the  veins 
in  the  liver  see  p.  262.) 

The  lobes  of  the  liver  develop  in  a  general  way  in  relation  to  the  great 
venous  trunks  which  at  one  time  or  another  pass  into  or  through  the  gland. 
The  anlage  of  the  organ  grows  into  the  ventral  mesentery,  subsequently  be- 
coming enclosed  in  the  septum  transversum.  In  so  doing  it  encounters  the 
omphalomesenteric  veins,  and  forms,  in  relation  to  the  latter,  two  incompletely 
separated  parts  which  have  been  called  the  dorso-lateral  lobes.  When  the 
umbilical  veins  enter  the  liver  a  more  ventral,  medial  mass  is  formed.  This 
becomes  incompletely  separated  into  two  parts  which  give  rise  to  the  permanent 


350  TEXT-BOOK  OF  EMBRYOLOGY. 

right  and  left  lobes.  The  right  becomes  the  larger.  The  right  umbilical  vein 
loses  its  connection  with  the  liver  (p.  264).  After  birth  the  left,  which  lies  be- 
tween the  right  and  left  lobes,  degenerates  into  the  round  ligament  of  the  liver. 
The  other  lobes  arise  secondarily  as  outgrowths  from  the  right  primary  dorso- 
lateral  lobe,  the  caudate  (lobe  of  Spigelius)  from  its  inner  (medial)  surface, 
the  quadrate  from  its  dorsal  surface. 

The  liver  as  a  whole  grows  rapidly  and  by  the  second  month  is  relatively 
large.  During  the  third  month  it  fills  the  greater  part  of  the  abdominal  cavity. 
After  the  fifth  month  it  grows  less  rapidly  and  the  other  intraabdominal  organs 
overtake  it,  so  to  speak,  although  at  birth  it  forms  one-eighteenth  the  total 
weight  of  the  body.  After  birth  it  actually  diminishes  in  size.  The  right  lobe 
is  from  the  beginning  larger  than  the  left,  and  after  birth  the  predominance 
increases.  • 

Histogenesis  of  the  Liver. — The  hepatic  part  (pars  hepatica)  of  the 
liver  anlage  is  derived  from  the  entodermal  lining  of  the  gut  and  constitutes  a 
mass  of  cells  with  no  lumen.  From  this  mass,  solid  bud-like  evaginations  grow 
into  the  mesentery,  break  up  the  omphalomesenteric  veins  into  smaller  channels 
and  form  trabeculae,  or  hepatic  cylinders  (p.  348).  The  latter  anastomose 
freely  with  one  another  and  are  composed  of  polyhedral,  darkly  staining  cells 
with  vesicular  nuclei  (Fig.  315,  A).  Lumina  begin  to  appear  in  the  cylinders 
about  the  fourth  week  as  small  cavities  which  communicate  with  the  cavity  of 
the  gut. 

The  hepatic  cylinders  are  the  forerunners  of  the  hepatic  cords  or  cords  of 
liver  cells.  There  are  two  views  as  to  the  manner  of  transformation.  -The 
older  view  is  that  the  cylinders  gradually  become  stretched,  the  number  of  cells 
in  cross-section  becoming  less  until  it  is  reduced  to  two.  Between  these  two 
lies  the  lumen  of  the  cord  or  the  so-called  "bile  capillary"  (Fig.  315,  B).  The 
other  view  is  that  branches  from  the  sinusoids  grow  into  the  cylinders  and  sub- 
divide them  into  hepatic  cords. 

As  stated  above,  the  hepatic  cylinders  are  at  first  composed  of  darkly  stain- 
ing, polyhedral  cells  with  vesicular  nuclei.  These  are  the  liver  cells  proper. 
Later  other  small  spherical  cells,  with  dense  nuclei,  appear  and  during  the 
fourth  month  become  very  numerous  (Fig.  315,  A).  From  this  time  on,  they 
grow  less  in  number  and  at  birth  have  practically  disappeared.  Earlier  investi- 
gators considered  them  as  developing  liver  cells.  Further  study  on  the  develop- 
ment of  the  blood,  however,  has  led  others  to  consider  them  as  erythroblasts 
(p.  271).  Since  they  are  inside  of  the  hepatic  cylinders,  they  either  wander  in 
from  the  intertrabecular  blood  vessels  or  lie  in  intratrabecular  vessels.  The 
latter  supposition  accords  with  the  view  that  the  cylinders  are  broken  up  into 
hepatic  cords  by  the  ingrowth  of  branches  from  the  sinusoids. 

The  development  of  the  lobules  of  the  liver,  producing  the  peculiar  relations 


DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGANS.   351 


between  the  parenchyma  of  the  gland  and  the  blood  vessels,  has  not  been 
clearly  and  completely  demonstrated.  In  young  embryos  the  branches  of  the 
hepatic  veins  are  surrounded  by  comparatively  little  connective  tissue.  The 
branches  of  the  portal  vein  are  surrounded  by  a  considerable  amount  which 
subdivides  the  liver  into  lobules  but  not  in  the  same  manner  as  in  the  adult. 
The  trabeculae  possess  no  radial  character  and  there  are  several  so-called  central 
veins  in  each  lobule.  The  changes  by  which  these  primary  lobules  are  sub- 
divided into  the  permanent  ones  do  not  take  place  until  after  birth.  The 
branches  of  the  portai  vein,  with  the  surrounding  connective  tissue,  invade  the 


FIG.  315. — Sections  of  the  liver  of  (^4)  a  human  foetus  of  6  months  and  (B)  a  child  of  4  years. 

Toldt  and  Zuckerhandl.  McMurrich. 
be,  Bile  "capillary";  e,  erythroblast;  he,  hepatic  cylinder  (in  A),  cord  of  liver  cells  (in  B). 

primary  lobules  and  divide  them  into  a  number  of  secondary  lobules,  corre- 
sponding to  the  original  number  of  central  veins.  At  the  same  time  the  hepatic 
cords  (which  have  been  formed  meanwhile)  become  arranged  radially  around 
the  central  veins  in  the  characteristic  manner.  The  hepatic  artery  grows  into 
the  liver  secondarily  and  its  branches  follow  the  course  of  the  branches  of  the 
portal  vein. 

Degeneration  of  the  liver  cells  occurs  in  the  region  of  the  left  triangular  liga- 
ment, the  gall  bladder  and  the  inferior  vena  cava.  The  bile  ducts  may,  how- 
ever, withstand  the  degenerative  processes  and  persist  as  the  vasa  aberrantia  of 
the  liver.  The  cause  of  the  degeneration  is  possibly  the  pressure  brought  to 
bear  by  other  organs. 

The  Development  of  the  Pancreas. 

The  epithelium  of  the  pancreas,  like  that  of  the  liver,  is  a  derivative  of  the 
entoderm.  It  arises  from  two  (or  three)  separate  anlagen,  one  dorsal  and  one 

23 


352 


TEXT-BOOK  OF  EMBRYOLOGY. 


(or  two)  ventral.  The  dorsal  anlage  appears  first  as  a  ridge-like  evagination 
from  the  dorsal  wall  of  the  gut,  slightly  cranial  to  the  level  of  the  liver  (Figs.  311 
and  312).  It  appears  about  the  same  time  as  the  liver  or  a  little  later.  The 
mass  of  cells  grows  into  the  dorsal  mesentery  and  becomes  constricted  from 
the  parent  epithelium  except  for  a  thin  neck  which  becomes  the  duct  of 
Santorini  (Fig.  316).  A  little  later  two  other  diverticula  appear,  one  from  each 
side  of  the  common  bile  duct.  It  is  uncertain  whether  only  one  or  both  of  these 


Stomach 


Dorsal  pancreas ' 


Acces.  pancr. 
duct  (oantorini) 


Dorsal  pancreas 


Cystic  duct 


Gall  bladder 

Ductus  choledochus 
Ventral  pancreas 


Dorsal  pancreas 

Acces.  pancr.  duct 
(Santorini) 


Duodenum 


Ductus  choledochus 


Liver 


Cystic  duct 


Gall  bladder 


Ventral  pancreas  with 
pancr.  duct  (Wirsung) 
FIG.  317. 

FIGS.  316  and  317. — From  models  of  the  developing  liver  and  pancreas  of  rabbit  embryos  of 
8  mm.  and  10  mm.,  respectively.     Both  seen  from  the  right  side.     Hammar,  Bonnet. 

take  part  in  -the  formation  of  the  pancreas,  but  it  seems  most  probable  that  the 
left  one  disappears  entirely.  The  right  diverticulum  continues  to  develop  and 
becomes  constricted  from  the  parent  epithelium,  leaving  only  a  thin  neck  which 
becomes  the  duct  of  Wirsung. 

The  smaller  ventral  pancreas  grows  to  the  right  and  then  dorsally  in  the 
mesentery  (Fig.  318),  passing  over  the  right  surface  of  the  portal  vein,  until  it 
meets  and  fuses  with  the  proximal  part  of  the  larger  dorsal  pancreas.  The 
fusion  takes  place  in  the  sixth  week,  and  the  two  anlagen  then  form  a  single 


DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGANS.      353 

mass.  A  communication  is  established  between  the  two  ducts,  and  the  dorsal 
duct  (Santorini)  usually  disappears,  leaving  the  ventral  (Wirsung)  as  the  per- 
manent duct  opening  into  the  ductus  choledochus.  In  a  general  way  it  may  be 
said  that  the  ventral  anlage  gives  rise  to  the  head,  the  dorsal  anlage  to  the  body 
and  tail  of  the  pancreas  (compare  Figs.  316  and  317). 

As  the  pancreas  grows  into  the  dorsal  mesentery  it  comes  to  lie  in  the 
dorsal  mesogastrium  between  the  greater  curvature  of  the  stomach  and  the 
vertebral  column,  and  since  the  dorsal  mesogastrium  at  first  lies  in  the  medial 
sagittal  plane,  the  pancreas  is  similarly  situated.  After  the  sixth  week,  how- 
ever, as  the  stomach  changes  its  position  (p.  337),  the  pancreas  is  carried  along 


Inf.  vena  cava 

Ccelom 

Dorsal  pancreas 

Portal  vein 

Ventral  pancreas 

Ductus  choledochus 

Right  side 


Mesonephros 


Greater  omentum 
(dorsal  mesentery) 


Duodenum 


Liver 


Left  side 


FIG.  318. — From  a  transverse  section  through  the  region  of  the  duodenum  of  a  pig 
embryo  of  14  mm.     Photograph. 


with  the  mesogastrium  and  comes  to  lie  in  a  transverse  plane,  with  its  head  to 
the  right  and  embedded  in  the  bend  of  the  duodenum,  and  its  tail  reaching  to 
the  spleen  on  the  left.  The  organ  as  a  whole  is  at  first  movable  along  with  the 
mesentery,  but  when  it  assumes  its  transverse  position  it  lies  close  to  the  dorsal 
abdominal  wall.  The  mesentery  then  fuses  with  the  adjacent  peritoneum 
(see  p.  382),  and  the  pancreas  is  firmly  fixed. 

The  connective  tissue  of  the  pancreas  is  derived  from  the  mesodermal  tissue 
of  the  mesentery.  As  the  processes  or  buds  which  form  the  ducts  and  terminal 
tubules  grow  out  from  the  primary  masses,  they  penetrate  the  mesodermal 
tissue  and  are  surrounded  by  it.  Groups  of  tubules  form  lobes  and  lobules, 
and  the  entire  gland  is  surrounded  by  a  capsule  of  connective  tissue. 


354 


TEXT-BOOK  OF  EMBRYOLOGY. 


Histogenesis  of  the  Pancreas. — The  masses  of  entodermal  cells  forming 
the  anlagen  of  the  pancreas  develop  further  by  a  process  of  budding,  which 
goes  on  until  finally  a  compound  tubular  gland  is  produced.  According  to 


lz 


FIG.  319. — Sections  of  the  developing  pancreas  of  a  guinea-pig  embryo  of  12  mm.  (a); 

of  33  mm.  (&);  of  Torpedo  marmorata  (c).     Hetty. 

c,  Capillaries;  Dg,  ducts;  Gz,  duct  cells;  Lz,  Langhans"    cells.     The  cells  in  c  show 
distinct  zymogen  granules 

some  investigators  the  primary  evaginations  are  hollow,  their  lumina  being  , 
continuous  with  the  lumen  of  the  gut.     According  to  others  they  are  solid  at 
first  and  acquire  their  lumina  secondarily.     The  same  uncertainty  exists  in 
regard  to  the  later  outgrowths  or  buds. 


DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGANS.   355 

The  early  entodermal  cells  proliferate,  and  the  resulting  cells  change  ac- 
cording to  their  position  in  the  gland.  Those  lining  the  larger  ducts  become 
high  columnar,  with  more  or  less  homogeneous  cytoplasm;  those  lining  the 
intermediate  (intercalated)  ducts  become  low;  those  lining  the  terminal  secret- 
ing tubules  become  pyramidal  and  more  highly  specialized,  and  also  acquire 
certain  constituents — the  zymogen  granules  (Fig.  319,  c) — which  vary  with  the 
functional  activities  of  the  gland.  The  centro-tubular  cells  in  the  terminal 
tubules  are  probably  to  be  explained  on  a  developmental  basis.  While  a  few 
maintain  that  they  are  "wandering"  cells,  it  is  quite  generally  accepted 
that  they  are  simply  continuations  of  the  flat  cells  lining  the  intermediate 
ducts,  the  result  being  that  the  cells  of  the  terminal  tubules  seem  to 
spread  out  over  the  ends  of  the  intermediate  ducts  in  the  form  of  cap-like 
structures. 

It  was  once  thought  that  the  islands  of  Langerhans  were  derived  from  the 
mesodermal  tissue.  Recently  it  has  been  pretty  clearly  demonstrated  that  they 
are  derived  from  entoderm.  In  guinea-pig  embryos  of  5  to  6  mm.,  at  a  time 
when  the  dorsal  pancreas  has  merely  begun  its  constriction  from  the  gut,  certain 
cells  in  the  mass  appear  darker  and  slightly  larger  than  the  others.  They  show 
darker  areas  of  cytoplasm  around  the  nuclei,  and  later  the  darker  areas  extend 
throughout  the  cells  and  the  nuclei  become  larger  and  more  vesicular.  When 
lumina  appear  in  the  outgrowths  or  buds,  these  cells  occupy  a  position  on  or  near 
the  surface  of  the  buds  (Fig.  319,  a).  In  further  development  they  tend  to  sepa- 
rate themselves  from  the  buds  and  collect  in  clumps  (Fig.  319,  b).  Capillaries 
then  penetrate  the  clumps  and  break  them  up  into  the  trabeculae  of  cells  char- 
acteristic of  the  islands  of  Langerhans  (Fig.  319,  c).  Studies  on  the  development 
of  the  islands  in  the  human  pancreas  indicate  a  similar  origin  and  mode  of 
development. 

Anomalies. 

One  of  the  most  striking  anomalies  of  the  organs  of  alimentation  is  found 
in  connection  with  a  more  general  anomalous  condition  known  as  transposition 
of  the  viscera  (situs  viscerum  in  versus) .  The  transposition  may  be  so  complete 
that  the  minor  asymmetries  normally  present  on  the  two  sides  are  all  repeated 
in  reverse  order,  the  functions  of  the  organs  being  unimpaired.  As  regards  the 
alimentary  tract,  this  means  that  the  position  of  the  stomach  is  reversed  in  the 
abdominal  cavity;  that  the  duodenum  crosses  from  left  to  right;  that  the  various 
coils  of  the  jejunum  and  ileum  occupy  positions  opposite  to  the  normal;  that  the 
caecum  and  ascending  colon  are  situated  on  the  left  side  and  the  descending 
colon  on  the  right;  and  that  the  larger  lobe  of  the  liver  lies  on  the  left  side.  The 
other  visceral  organs  are  transposed  accordingly,  the  heart  being  inclined  to- 
ward the  right  side,  the  left  lung  consisting  of  three  lobes  and  the  right  of  two, 


356  TEXT-BOOK  OF  EMBRYOLOGY. 

the  left  kidney  being  lower  than  the  right,  etc.  Such  cases  are  not  uncommon, 
two  hundred  being  on  record. 

Various  theories  as  to  the  causes  of  transposition  of  the  organs  have  been 
advanced.  In  the  most  plausible  of  these  the  anomalous  condition  is  consid- 
ered as  due  to  the  influence  of  the  large  veins  in  the  embryo.  It  seems  best, 
therefore,  to  consider  first  the  transposition  of  the  heart  (dextrocardia,  referred 
to  on  page  285). 

After  the  two  anlagen  unite  in  the  midventral  line,  the  heart  constitutes  a 
simple  straight  tube  which  lies  in  a  longitudinal  direction  in  the  primitive  peri- 
cardial  cavity,  and  which  is  joined  caudally  by  the  two  omphalomesenteric 
veins  and  cranially  by  the  ventral  aortic  trunk  (p.  224).  Normally  the  left 
omphalomesenteric  vein  is  the  larger  and  pours  a  greater  quantity  of  blood  into 
the  heart  tube  than  the  right.  This  condition  is  regarded  as  the  primary  factor 
in  the  deflection  of  the  tube  toward  the  right  side  (p.  226;  also  Fig.  196).  If  the 
conditions  were  reversed,  that  is,  if  the  right  omphalomesenteric  vein  were  the 
larger  and  poured  the  greater  quantity  of  blood  into  the  heart  tube,  the  pri- 
mary bend  of  the  latter  would  be  toward  the  left  side.  Consequently  the  heart 
would  continue  to  develop  in  the  transposed  position  and  eventually  come  to 
lie  on  the  side  opposite  to  the  normal. 

Although  dextrocardia  is  very  frequently  associated  with  transposition  of 
the  abdominal  organs,  it  is  not  necessarily  so,  for  there  are  cases  of  the  latter  in 
which  the  heart  occupies  the  normal  position.  Consequently  it  seems  that 
further  influences  must  be  present  to  account  for  transposition  of  the  abdominal 
organs  when  the  thoracic  organs  are  normal.  A  number  of  investigators  have 
emphasized  the  importance  of  the  influence  of  the  large  venous  trunks  in  the 
abdominal  region,  especially  on  the  position  of  the  liver  and  stomach. 

Primarily  the  omphalomesenteric  veins  pass  cranially  through  the  mesen- 
tery. Later  they  form  two  loops  or  rings  around  the  duodenum.  Then  the 
left  half  of  the  upper  ring  and  the  right  half  of  the  lower  disappear,  the  common 
venous  trunk  thus  following  a  spiral  course  around  the  duodenum  (p.  265;  also 
Fig.  239).  This  primary  relation  of  the  omphalomesenteric  vein  is  retained  in 
the  relation  of  the  portal  vein  to  the  duodenum.  The  stomach  lies  to  the  left 
of  the  portal  vein.  After  the  allantoic  (placental)  circulation  is  established  the 
umbilical  veins  pass  cranially  in  the  lateral  body  walls.  After  the  veins  come 
into  connection  with  the  liver,  the  right  atrophies  and  the  left  increases  in  size 
and  becomes  the  single  large  umbilical  vein  of  later  stages  (p.  264;  also  Fig.  240). 
The  right  lobe  of  the  liver  becomes  the  larger. 

If,  as  is  maintained  by  some  investigators,  the  usual  position  of  the  stomach 
and  liver  is  due  to  the  persistence  of  the  left  venous  trunks,  a  persistence  of  the 
right  venous  trunks  would  afford  a  plausible  explanation  of  the  transposition  of 
these  organs.  It  is  not  unreasonable  to  attribute  also  the  transposition  of  the 


DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGANS.      357 

other  abdominal  organs  directly  or  indirectly  to  the-  persistence  of  the  right 
venous  trunks.  Certainly  a  reversal  in  the  position  of  the  stomach  would 
cause  a  reversal  in  the  position  of  the  duodenum. 

If  these  conditions  are  the  real  ones,  the  fact  that  the  thoracic  organs  can  be 
transposed  without  a  transposition  of  the  abdominal  organs,  or  vice  versa, 
is  accounted  for.  The  primary  bend  of  the  heart  tube  occurs  at  a  very  early 
period,  before  the  changes  in  the  vessels  in  the  region  of  the  liver.  Conse- 
quently a  reversal  of  the  conditions  of  the  omphalomesenteric  at  a  very  early 
stage  only  would  be  likely  to  affect  the  heart.  The  principal  changes  in  size 
of  the  venous  trunks  in  the  abdominal  region  take  place  after  their  channels 
have  been  broken  up  in  the  liver.  In  other  words,  the  modifications  in  the  veins 
in  the  liver  occur  after  the  definite  relations  of  the  heart  have  been  established. 
Therefore  the  transposition  of  the  abdominal  organs  may  take  place  after  the 
heart  has  begun  to  develop  normally. 

THE  MOUTH. — Anomalies  in  the  mouth  region,  due  to  defective  fusion  of 
the  processes  that  bound  it,  have  been  considered  elsewhere  (p.  216). 

Anomalies  of  the  tongue  sometimes  arise  as  the  result  of  imperfect  develop- 
ment of  one  or  more  of  its  anlagen.  Imperfect  development  of  the  tuberculum 
impar  results  in  total  or  partial  lack  of  the  anterior  part.  Defects  in  the  root 
are  probably  due  to  imperfect  development  of  one  or  both  of  the  paired  anlagen 
(p.  321).  Malformations  of  the  lower  jaw  (micrognathus,  agnathus)  are 
usually  accompanied  by  malformations  of  the  tongue,  both  structures  being 
derived  largely  from  the  first  pair  of  branchial  arches. 

THE  PHARYNX. — The  pharynx  is  the  seat  of  cysts,  fistulas  and  diverticula 
which  have  been  considered  in  connection  with  the  anomalies  in  the  region  of 
the  branchial  arches  and  grooves  (Chap.  XIX). 

The  thyreoid  gland  is  not  infrequently  the  seat  of  certain  anomalies  that 
arise  as  the  result  of  abnormal  development.  Persistent  portions  of  the  thyreo- 
glossal  duct,  the  upper  end  of  which  is  indicated  by  the  foramen  caecum  linguae, 
may  give  rise  to  cystic  structures  extending  to  the  region  of  the  hyoid  bone. 
Persistent  portions  of  the  duct  may  even  give  rise  to  accessory  thyreoid  (supra- 
hyoid,  prehyoid)  glands  (p.  333;  also  Fig.  298).  Considerable  variation  also 
exists  in  the  isthmus  and  lateral  lobes  of  the  thyreoid,  due  to  variation  in  the 
manner  of  development  of  the  medial  anlage. 

Impaired  development  of  the  thymus  gland  sometimes  leads  to  cysts  which 
come  to  lie  in  the  anterior  mediastinum. 

THE  (ESOPHAGUS. — Very  rarely  the  oesophagus  is  entirely  lacking,  being 
represented  by  a  mere  cord  of  tissue.  More  frequently  it  is  defective  in  certain 
parts.  The  atresia  may  begin  just  below  the  pharynx  or  just  above  the  stomach, 
the  intermediate  portion  being  composed  of  a  cord  of  fibrous  tissue.  Occasion- 
ally the  non-atretic  portion  opens  into  the  trachea.  Possibly  this  represents 


358  TEXT-BOOK  OF  EMBRYOLOGY. 

an  imperfect  separation  between  the  primitive  gut  and  the  anlage  of  the 
respiratory  system  (p.  362). 

THE  STOMACH. — Occasionally  the  stomach  is  smaller  than  the  normal.  It 
may  even  be  a  narrow  tube  resembling  the  other  portions  of  the  gut,  owing  to 
lack  of  dilatation.  Other  congenital  malformations,  apart  from  transposition 
(p.  355),  are  very  rare. 

THE  INTESTINES. — One  of  the  most  common  anomalies  is  the  persistence  of 
the  proximal  end  of  the  yolk  stalk,  forming  Meckel's  diverticulum  (see  p.  117). 
This  usually  is  attached  to  the  ileum  about  three  feet  from  the  caecum.  In  ex- 
ceptional cases  it  retains  its  lumen  and,  when  the  stump  of  the  umbilical  cord 
disappears,  forms  a  congenital  umbilical  fistula.  Usually,  however,  the  diver- 
ticulum is  shorter  and  ends  blindly.  Occasionally  it  becomes  constricted  from 
the  intestine  and  forms  a  cystic  structure.  (See  also  Chap.  XIX.) 

Congenital  stenosis  and  atresia  may  occur  in  different  regions  of  the  intestine, 
the  duodenum  being  the  most  common  site.  Normally  the  lumen  of  the 
duodenum  becomes  closed  for  a  brief  period  during  development  (p.  339),  and 
congenital  closure  of  the  lumen  may  represent  a  persistence  of  the  early  em- 
bryonic condition. 

A  conspicuous  malformation  is  the  persistence  of  the  cloaca.  The  septum 
which  normally  separates  the  latter  structure  into  rectum  and  urogenital  sinus 
fails  to  develop,  thus  leaving  a  common  cavity  (see  Figs.  361  and  362).  In 
addition  to  this  the  cloacal  membrane  may  fail  to  rupture  and  the  cloaca  be- 
come much  distended.  More  often  the  septum  develops  in  part,  leaving  only 
a  small  opening  between  the  rectum  and  urogenital  sinus.  After  the  latter 
undergoes  further  development,  the  rectum  comes  to  open  into  the  urethra  or 
bladder,  or  into  the  vagina  or  uterus. 

Atresia  of  the  anus  is  not  infrequently  met  with.  The  cloacal  (or  anal) 
membrane  fails  to  rupture  and  the  rectum  ends  blindly.  In  other  cases  the 
rectum  opens  into  the  urogenital  sinus,  as  described  in  the  preceding  paragraph. 
Occasionally  the  lumen  of  the  rectum  is  closed — atresia  recti — and  the  gut  ends 
blindly  some  distance  from  the  surface,  being  connected  with  the  anal  region  by 
a  cord  of  fibrous  tissue. 

Variations  in  the  position  of  the  intestinal  loops,  apart  from  transposition  (p. 
355),  are  of  frequent  occurrence.  It  is  not  customary  to  include  these  varia- 
tions among  malformations  (see  p.  340).  The  caecum  (and  appendix)  and  colon 
present  some  striking  variations.  The  caecum  may  be  situated  high  up  in  the 
abdominal  cavity,  the  ascending  colon  being  absent.  Or  it  may  be  situated  at 
any  intermediate  point  between  that  and  its  usual  position  in  the  right  iliac 
fossa.  These  variations  are  due  to  different  degrees  of  development  of  the 
ascending  colon  (p.  341). 

THE  LIVER. — Congenital  malformations  of  the  liver  are  rare.     The  most 


DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGANS.   359 

frequent,  apart  from  transposition,  include  anomalies  in  the  size  and  number  of 
lobes.  Accessory  lobes  may  occur  within  the  falciform  ligament.  One  case 
of  lack  of  development  of  the  gall  bladder  has  been  observed.  Stenosis  of  the 
bile  passages  is  occasionally  met  with. 

THE  PANCREAS. — Occasionally  accessory  glands  are  found  in  the  intesti- 
nal or  gastric  wall.  These  probably  represent  aberrant  portions  of  the  main 
gland,  and  may  give  rise  to  cystic  structures.  Very  recently,  however,  a 
number  of  intestinal  diverticula  have  been  observed  in  certain  mammalian 
embryos  and  also  in  human  embryos.*  Although  the  history  of  these  unusual 
diverticula  has  not  been  traced,  their  presence  may  offer  a  clue  to  the  origin  of 
accessory  pancreatic  structures.  The  ducts  of  the  pancreas  are  subject  to 
distinct  variations,  which,  however,  are  not  usually  considered  as  anomalies. 
Not  infrequently  the  duct  of  the  dorsal  anlage  (duct  of  Santorini)  persists  and 
opens  directly  into  the  duodenum.  It  may  persist  along  with  the  duct  of  the 
ventral  anlage  (duct  of  Wirsung),  or  the  latter  may  disappear  (p.  353;  compare 
Figs.  316  and  317). 

PRACTICAL  SUGGESTIONS. 

The  Primitive  Gut. — The  formation  of  the  primitive  gut  can  be  studied  in  chick  embryos 
prepared  according  to  the  technic  on  page  385,  under  the  head  of  the  Ccelom  and  Common 
Mesentery. 

The  Mouth  and  Pharynx. — The  external  appearance  of  the  oral  pit  and  the  branchial 
arches  and  grooves  can  be  studied  in  very  young  pig  embryos  (6  mm.  or  less).  The  speci- 
mens should  be  preserved  in  toto  in  4  per  cent,  formalin,  and  for  class  purposes  can  be 
mounted  in  glycerin  jelly  (see  Appendix).  Occasionally  young  human  embryos  (8  mm. 
or  less)  are  obtained,  in  which  the  branchial  arches  and  grooves  show  clearly. 

For  the  study  of  the  internal  structure,  sections  of  course  are  necessary.  Pig  embryos 
afford  very  good  material  and  are  easily  obtained.  The  specimens  may  be  fixed  in  Zenker's 
or  Bouin's  fluid,  cut  in  celloidin  or  in  paraffin,  and  stained  with  haematoxylin  and  eosin. 
Usually  it  is  advisable  to  cut  serial  sections.  The  stages  given  in  the  following  paragraphs 
are  perhaps  the  most  convenient  for  the  study  of  the  different  organs. 

The  tongue  can  be  seen  in  its  earlier  stages  in  sagittal  sections  of  pig  embryos  of  12  to 
18  mm.  The  development  of  the  teeth  can  be  followed  in  embryos  of  20  to  100  mm.  The 
most  convenient  way  is  to  remove  the  jaws,  fix  for  several  days  in  Bouin's  fluid,  which 
at  the  same  time  decalcifies,  and  cut  sections  transversely  to  the  long  axes  of  the  jaws. 
Very  beautiful  preparations  can  be  obtained  in  this  way.  The  anlagen  of  the  salivary  glands 
can  be  seen  in  embryos  of  15  mm.  The  anlagen  of  the  thyreoid  and  thymus  are  very  clearly 
shown  in  embryos  of  10  to  15  mm. 

The  cesophagus  can  be  seen  in  any  transverse  section  in  the  thoracic  region  of  an  embryo 
of  any  stage  after  the  formation  of  the  primitive  gut. 

The  Stomach  and  Intestine. — The  development  of  these  organs  can  be  studied  in  transverse 
sections  of  pig  embryos  of  from  6  mm.  up  to  any  size  that  is  not  too  large  to  section.  Zenker's 
and  Bouin's  fluid  are  both  good  fixatives.  It  is  best  to  cut  transverse  serial  sections, 
although  sections  taken  at  intervals  are  very  instructive.  Haematoxylin  and  eosin  give  a 

*  Lewis.  Thyng. 


360  TEXT-BOOK  OF  EMBRYOLOGY. 

good  differential  stain.  The  later  stages  of  development  can  be  followed  in  very  carefully 
made  gross  dissections.  Wax  reconstructions  of  one  or  two  of  the  earlier  stages  are  useful. 
These  can  be  made  in  conjunction  with  reconstructions  of  the  mesenteries  (p.  385). 

The  Liver  and  Pancreas. —  Very  young  embryos  (3  to  6  mm.)  are  necessary  in  studying 
the  primary  evaginations.  Transverse  sections  are  taken  just  cranial  to  the  umbilicus. 
Later  stages  can  be  studied  in  specimens  prepared  according  to  the  technic  in  the  preceding 
paragraph.  In  fact  the  same  sets  of  specimens  can  be  used  in  the  study  of  the  stomach, 
omenta,  duodenum,  liver,  and  pancreas,  since  these  structures  lie  so  nearly  in  the  same 
transverse  plane. 

The  htstogenesis  of  any  of  the  organs  of  alimentation  can  be  studied  after  the  technic 
given  above.  Histological  structure  is  well  preserved  by  Bouin's  fluid,  but  even  better  by 
Flemming's  fluid.  The  sections  should  be  cut  thin.  Hsematoxylin  and  eosin  give  a  good 
differential  stain  after  fixation  in  Bouin's  fluid.  After  Flemming's  fluid  Heidenhain's  haema- 
toxylin  should  be  used. 

References  for  Further  Study. 

BELL,  E.  T.:  The  Development  of  the  Thymus.     American  Jour,  oj  Anat.,  Vol.  V,  1906 

BERRY,  J.  M.:  On  the  Development  of  the  Villi  of  the  Human  Intestine.  Anat.  Anz. 
Bd.  XVI,  1900. 

BONNET,  R.:  Lehrbuch  der  Entwickelungsgeschichte.     Berlin,  1907. 

BORN,  G.:  Ueber  die  Derivate  der  embryonalen  Schlundbogen  und  Schlundspalten  bei 
Saugetiere.  Arch.  /.  mik.  Anat.,  Bd.  XXII,  1883. 

BRACKET,  A.:  Die  Entwickelung  und  Histogenese  der  Leber  und  des  Pancreas.  Ergeb- 
nisse  der  Anat.  u.  Entwick.,  Bd.  VI,  1897. 

CHIEVITZ,  J.  C.:  Beitrage  zur  Entwickelungsgeschichte  der  Speicheldrusen.  Arch.  f. 
Anat.  u.  Physiol.,  Anat.  Abth.,  1885. 

CHORONSCHITZKY:  Die  Entstehung  der  Milz,  Leber,  Gallenblase,  Bauchspeicheldriise 
und  des  Pfortadersystems  bei  den  verschiedenen  Abteilungen  der  Wirbeltiere.  Anat.  Hefte, 
Bd.  XIII,  1900. 

Fox,  H.:  The  Pharyngeal  Pouches  and  their  Derivatives  in  the  Mammalia.  Am.  Jour, 
of  Anat.,  Vol.  VIII,  No.  3,  1908. 

FUSARI,  R.:  Sur  les  phenomenes,  que  Ton  observe  dans  la  muqueuse  du  canal  digestif 
durant  le  developpement  du  foetus  humain.  Arch.  ital.  Biol.,  T.  XLII,  1904. 

GOPPERT,  E.:  Die  Entwickelung  des  Mundes  und  der  Mundhohle  mit  Driisen  und 
Zunge;  die  Entwickelung  der  Schwimmblase,  der  Lunge  und  des  Kehlkopfes  der  Wirbeltiere. 
In  Hertwig's  Handbuch  der  vergleich.  u.  experiment.  Ent-wickelungslehre  der  Wirbeltiere.  Bd. 
II,  Teil  I,  1902. 

HAMMAR,  J.  A.:  Einige  Plattenmodelle  zur  Beleuchtung  der  friiheren  embryonalen 
Leberentwickelung.  Arch.  /.  Anat.  u.  Physiol.,  Anat.  Abth.,  1893. 

HAMMAR,  J.  A.:  Allgemeine  Morphologie  der  Schlundspalten  beim  Menschen.  Entwick- 
elung des  Mittelohrraumes  und  des  ausseren  Gehorganges.  Arch.  /.  mik.  Anat.,  Bd.  LIX, 
1902. 

HAMMAR,  J.  A.:  Das  Schicksal  der  zweiten  Schlundspalte.  Zur  vergleichenden  Em- 
bryologie  und  Morphologie  der  Tonsille.  Arch.  /.  mik.  Anat.,  Bd.  LXI,  1903. 

HELLY,  K.:  Studien  iiber  Langerhanssche  Inseln.  Arch.  f.  mik.  Anat.,  Bd.  LXVII, 
1907. 

HERTWIG,  O. :  Lehrbuch  der  Entwickelungsgeschichte  der  Wirbeltiere  und  des  Menschen. 
Jena,  1906. 


DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGANS.   361 

HENDRICKSON,  W.  F.:  The  Development  of  the  Bile  Capillaries  as  Revealed  by  Golgi's 
Method.  Johns  Hopkins  Hosp.  Bull.,  1898. 

His,  W.:  Anatomic  menschlicher  Embryonen.     Leipzig,  1880-1885. 

His,  W.:  Die  Entwickelung  der  menschlichen  und  tierischen  Physiognomien.  Arch.  /. 
Anal.  u.  Physiol.,  Anal.  Abth.,  1892. 

KOHN,  A.:  Die  Epithelkorperchen.     Ergebnisse  der  Anat.  u.  Enlwick.,  Bd.  IX,  1899. 

KOLLMANN,  J.:  Die  Entwickelung  der  Lymphknotchen  in  dem  Blinddarm  und  in  dem 
Processus  vermiformis.  Die  Entwickelung  der  Tonsillen  und  die  Entwickelung  der  Milz. 
Arch.  }.  Anat.  u.  Physiol.,  Anat.  Abth.,  1900. 

KOLLMANN,  J.:  Lehrbuch  der  Entwickelungsgeschichte  des  Menschen.     Jena,  1898. 

KOLLMANN,  J.:  Handatlas  der  Entwickelungsgeschichte  des  Menschen.     Jena,  1907. 

MALL,  F.  P.:  Ueber  die  Entwickelung  des  menschlichen  Darmes  und  seiner  Lage  beim 
Erwachsenen.  Arch.  /.  Anat.  u.  Physiol.,  Anat.  Abth.  Suppl.,  1897. 

MAURER,  F.:  Die  Entwickelung  des  Darmsystems.  In  Hertwig's  Handbuch  der  ver- 
gleich.  u.  experiment.  Enlwickelungslehre  der  Wirbelliere.,  Bd.  II,  Teil  I,  1902. 

McMuRRiCH,  J.  P.:  The  Development  of  the  Human  Body.  Third  Ed.  Philadelphia, 
1907. 

PEARCE,  R.  M.:  The  Development  of  the  Islands  of  Langerhans  in  the  Human  Embryo. 
American  J  cur .  oj  Anat.,  Vol.  II,  1903. 

PIERSOL,  G.  A.:  Teratology.  In  Wood's  Reference  Handbook  o]  the  Medical  Sciences, 
Vol.  VII,  1904. 

POLZL,  A.:  Zur  Entwickelungsgeschichte  des  menschlichen  Gaumens.  Anat.  Hejte, 
1905. 

ROSE,  C.:  Ueber  die  Entwickelung  der  Zahne  des  Menschen.  Arch.  /.  mik.  Anat., 
Bd.  XXXVIII,  1891. 

STEIDA,  A.:  Ueber  Atresia  ani  congenita  und  die  damit  verbundenen  Missbildungen. 
Arch.  /.  klin.  Chir.,  Bd.  LXX,  1903 

STOHR,  P.:  Ueber  die  Entwickelung  der  Darmlymphknotchen  und  iiber  die  Ruckbildung 
von  Darmdriisen.  Arch.  /.  Anat.  u.  Physiol.,  Anat.  Abth.,  1898. 

TANDLER,  J.:  Zur  Entwickelungsgeschichte  des  menschlichen  Duodenum  in  friihen 
Embryonalstadien.  Morph.  Jahrb.,  Bd.  XXIX,  1900. 

TOLDT  und  ZUCKERHANDL:  Ueber  die  Form  und  Texturveranderungen  der  mensch- 
lichen Leber  wahrend  Wachsthums.  Sitzungsber.  d.  kaiser.  Akad.  d.  Wissensch.,  Wien. 
Math.-Naturuiss.  Klasse.,  Bd.  LXXII,  1875. 

TOURNEUX  ET  VERDUN:  Sur  les  premiers  developpements  de  la  Thyroide,  du  Thymus  et 
des  glandes  parathyroidiennes  chez  1'homme.  J  our.  de.V  Anat.  et.de  la  Physiol.,  T.  XXXIII, 
1897. 


CHAPTER  XIII. 


THE  DEVELOPMENT  OF  THE  RESPIRATORY  SYSTEM. 

The  anlage  of  the  respiratory  system  appears  in  human  embryos  of  about 
3.2  mm.  A  hollow,  linear  evagination — the  lung  groove — develops  on  the 
ventral  side  of  the  oesophageal  portion  of  the  primitive  gut,  extending  caudally 
a  short  distance  from  the  region  of  the  fourth  inner  branchial  groove.  It  was 
once  thought  that  the  evagination  developed  along  practically  the  entire  length 
of  the  oesophagus  anlage,  but  more  recent  researches  seem  to  prove  that  it  is 
confined  to  the  cephalic  end.  The  lung  groove  soon  becomes  separated  from 


Pharynx 


Branchial  arches 
(pharynx) 


Hypophysis    — 


Yolk  sac 


Mesonephros 


Allantoic  duct 


Hind-gut 


Belly  stalk    - 
Caudal  gut 

Kidney  bud  * 
FIG.  320. — Sagittal  section  of  reconstruction  of  a  human  embryo  of  5  mm.     His,  Kollmann. 

the  gut  by  a  constriction  which  appears  at  the  caudal  end  and  gradually  pro- 
gresses forward.  Thus  there  is  formed  a  tube  which  lies  ventral  to  the  gut  and 
which  opens  upon  the  floor  of  the  latter  at  the  boundary  line  between  the 
oesophagus  and  pharynx  (Figs.  320  and  284). 

From  this  simple  tube  the  entire  respiratory  system  develops.  The 
cephalic  end  gives  rise  to  the  larynx,  the  opening  into  the  gut  being  the  adltus 
laryngis.  The  middle  portion  gives  rise  to  the  trachea.  Two  outgrowths  from 
the  caudal  end  of  the  tube,  which  appear  about  the  time  of  separation  from  the 

362 


THE   DEVELOPMENT   OF  THE   RESPIRATORY  SYSTEM.  363 

oesophagus,  develop  into  the  bronchi  and  their  continuations— the  lungs.  The 
epithelial  lining  of  the  system  is  of  course  derived  from  the  entoderm.  The 
various  kinds  of  connective  tissue  are  derived  from  the  mesoderm,  since  the 
anlage  grows  into  the  mesodermal  tissue  of  the  ventral  mesentery. 

The  Larynx. 

The  opening  from  the  gut  into  the  respiratory  tube  becomes  surrounded  by 
a  U-shaped  elevation — thefurcula — which  lies  in  the  floor  of  the  pharynx  with 
its  open  end  directed  caudally.  Toward  the  end  of  the  first  month  each 
side  of  the  opening  (aditus  laryngis)  becomes  elevated,  forming  the  arytenoid 
ridge.  From  each  of  these  a  secondary  elevation  arises,  forming  the  cunei- 
form ridge.  The  arytenoid  ridges  come  so  close  together  that  they  practically 
close  the  opening  except  at  its  cephalic  side  (Fig.  321).  Along  with  the  develop- 
ment of  these  ridges  the  apical  portion  of  the  furcula  becomes  a  distinct  trans- 


Tuberculum  impar 


2s-  Epiglottis 

gg-  Aryepiglottic  ridge 

Arytenoid  ridge 


//$,[ Cuneiform  ridge 


Aditus  laryngis 
Cuneiform  ridge 


FIG.  321. — From  a  reconstruction  of  the  larynx  of  a  human  embryo  of  28  days. 
Seen  from  above.     Kallius. 

verse  fold  at  the  cephalic  rim  of  the  opening.  This  fold  is  the  anlage  of  the 
epiglottis.  Laterally  the  epiglottic  fold  becomes  continuous  with  the  arytenoid 
ridges,  forming  the  aryepiglottic  ridges  (Fig.  321). 

During  the  fourth  month  a  groove-like  depression  appears  on  the  medial 
side  of  each  arytenoid  ridge,  gradually  becomes  deeper,  and  leaves  on  each  side 
)f  it  a  fold  or  lip  which  bounds  the  opening.  The  external  lips — those  nearer 
the  pharynx — form  the  superior  or  false  vocal  cords;  the  internal  lips  form  the 
true  vocal  cords.  At  the  same  time  the  opening  into  the  larynx,  which  was 
closed  by  the  arytenoid  ridges,  is  reestablished.  The  depression  between  the 
vocal  cords  on  each  side  becomes  still  deeper  to  form  the  ventricle,  and  a  further 
outgrowth  from  the  ventricle  produces  the  appendage  of  the  ventricle  (the  laryn- 
geal  pouch). 


TEXT-BOOK  OF  EMBRYOLOGY. 


The  mesodermal  tissue  external  to  the  epithelium  (entoderm)  of  the  larynx 
gives  rise  to  the  various  kinds  of  connective  tissue  including  the  laryngeal 
cartilages.  By  the  end  of  the  fourth  week  condensations  appear  in  the  mesen- 
chymal  tissue,  which  are  the  forerunners  of  the  cartilages,  but  true  cartilage 
does  not  appear  until  the  seventh  week.  The  anlagen  of  the  thyreoid  cartilage 

Sup.  hy. 


Sup.  hy. 


-    Thyr. 


Inf.  hy. 


Thyr. 


FIG  322. — From  reconstructions  of  the  mesenchymal  condensations  which  represent  the  hyoid  and 
thyreoid  cartilages  in  an  embryo  of  40  days.  A,  Ventral  view;  B,  lateral  view  from  right. 
Kallius. 

Inf.hy.,  Inferior  (greater)  horn  of  hyoid;  Sup.hy.,  superior  (lesser)  horn  of  hyoid;  Thyr.,  thyreoid. 
The  portions  indicated  by  black  lines  represent  chondrification  centers. 

are  two  mesenchymal  plates,  one  on  each  side,  which  are  bilaterally  sym- 
metrical and  correspond  to  the  lateral  parts  of  the  adult  cartilage  (Fig.  322,  A). 
These  plates  gradually  grow  ventrally  and  unite  and  fuse  in  the  midventral 
line  (Fig.  323).  Twocentersof  chondrification  appear  in  each  plate  (Fig.  322, .4,) 


_••_       Pharynx 


Muscle 


Arytenoid  cartilage 


'- —  Thyreoid  cartilage 


Muscle 


Copula 

FIG.  323. — From  a  transverse  section  through  the  pharynx  and  larynx  of  a  human 
embryo  of  48  mm.     Nicolas. 

and  enlarge  until  the  entire  plate  is  converted  into  cartilage,  the  middle  part 
becoming  elastic  in  character,  the  rest  hyalin. 

Originally  the  cephalic  edge  of  each  thyreoid  plate  is  connected  with  the 
inferior  horn  of  the  hyoid  cartilage  (Fig.  322,  B).  This  connection  is  subse- 
quently lost,  but  a  remnant  of  the  connecting  cartilage  persists  as  the  triticeous 


THE  DEVELOPMENT   OF  THE   RESPIRATORY  SYSTEM.  365 

cartilage  in  the  lateral  hyothyreoid  ligament.  The  anlagen  of  the  arytenoid 
cartilages  develop  in  the  arytenoid  ridges  as  condensations  of  the  mesenchyme, 
which  later  are  converted  into  true  cartilage  (Fig.  323).  The  apex  and  vocal 
process  of  each  arytenoid  become  elastic,  the  main  body  becomes  hyalin. 
The  corniculate  cartilages  (cartilages  of  Santorini)  are  split  off  from  the  cephalic 
ends  of  the  arytenoids  and  are  of  the  elastic  variety.  The  cricoid  cartilage, 
like  the  others,  is  preceded  by  a  condensation  of  mesenchyme.  Chondrifica- 
tion  begins  on  each  side  and  then  progresses  around  dorsally  and  ventrally  until 
a  complete  hyalin  ring  is  formed.  From  its  developmental  resemblance  to  the 
tracheal  rings,  the  cricoid  is  sometimes  regarded  as  the  most  cephalic  of  that 
series.  The  epiglottic  cartilage  develops  in  the  epiglottic  ridge  as  two  sepa- 
rate pieces  which  subsequently  fuse.  It  is  of  the  elastic  variety.  The  cuneiform 
cartilages  (cartilages  of  Wrisberg)  are  split  off  from  the  two  pieces  of  the  epi- 
glottic, and  are  of  the  elastic  type. 

Attempts  have  been  made  to  determine  which  branchial  arches  are  represented  by  the 
laryngeal  cartilages.  It  seems  quite  definitely  settled  that  the  thyreoid  is  derived  in  part,  at 
least,  from  the  fourth  arch.  There  is  much  doubt  as  regards  the  others,  for  there  is  great 
difficulty  in  determining  their  derivation  in  the  human  embryo,  since  the  arches  disappear 
at  such  an  early  stage.  Furthermore,  some  of  these  cartilages  may  represent  arches  which 
are  present  in  lower  forms  but  do  not  appear  in  the  higher  Mammals. 

The  larynx  is  situated  much  farther  cranially  in  the  foetus  and  in  the  new- 
born child  than  in  the  adult.  In  a  five  months  foetus  it  extends  into  the  naso- 
pharyngeal  cavity,  whence  it  migrates  caudally  to  its  adult  position.  The 
laryngeal  skeleton  becomes  ossified  during  postnatal  life.  Ossification  begins 
in  the  thyreoid  and  cricoid  cartilages  at  the  age  of  eighteen  to  twenty  years, 
and  in  the  arytenoids  a  few  years  later.  Three  centers  appear  in  the  thyreoid 
— one  on  each  side  near  the  inferior  cornu  and  one  in  the  medial  line  between 
the  two  wings.  In  the  cricoid,  ossification  begins  near  the  upper  border  on 
each  side,  in  the  arytenoids  at  the  lower  borders.  Ossification  usually  begins 
earlier  and  proceeds  more  rapidly  in  the  male  than  in  the  female. 

As  an  example  of  the  explanation  which  Embryology  offers  of  certain  peculiarities  of 
structure  in  the  adult,  the  case  of  the  recurrent  laryngeal  nerve  may  be  cited.  The  heart  and 
aortic  arches  are  primarily  situated  in  the  cervical  region.  At  that  time  a  branch  of  the 
vagus  on  each  side,  passes  behind  the  fourth  aortic  arch  to  reach  the  larynx.  As  the 
heart  and  arches  recede  into  the  thorax,  the  nerve  is  pulled  caudally  between  its  origin  and 
termination,  so  that  in  the  adult  the  left  nerve  bends  around  the  arch  of  the  aorta  and  the 
right  around  the  subclavian  artery. 

The  Trachea. 

The  portion  of  the  original  tube  between  the  larynx  and  the  twTo  caudal  out- 
growths which  form  the  bronchi  and  lungs,  develops  into  the  trachea.  It  lies 
ventral  to  the  oesophagus  and  is  surrounded  by  mesodermal  tissue  which  is 


366 


TEXT-BOOK  OF  EMBRYOLOGY. 


destined  to  give  rise  to  the  connective  tissue,  includng  the  cartilage,  of  the  adult 
trachea  (Figs.  284  and  320).  The  development  of  the  tracheal  rings  is  very 
similar  to  that  of  the  laryngeal  cartilages.  During  the  eighth  or  ninth  week  con- 
densations appear  in  the  mesenchyme,  which  are  later  transformed  into  hyalin 
cartilage.  The  rings  are  not  complete  but  remain  open  on  the  dorsal  side.  At 
birth  the  trachea  is  collapsed,  the  ventral  side  being  concave  and  the  dorsal  ends 
of  each  ring  being  in  contact.  After  respiration  begins  it  is  dilated  and  becomes 
more  or  less  rigid.  Ossification  of  the  tracheal  rings  begins  in  the  male  at  the 
age  of  about  forty  years,  in  the  female  at  about  sixty.  The  glands  of  the 
trachea  represent  evaginations  from  the  epithelial  linings. 

The  Lungs. 

As  has  been  stated  (p.  362),  the  caudal  end  of  the  original  tube  evaginates 
to  form  two  hollow  buds  which  are  the  beginnings  of  the  two  lungs  (Fig.  324). 
The  evagination  takes  place  soon  after  or  even  along  with  the  separation  of  the 
lung  groove  from  the  gut.  The  right  bud  soon  gives  rise  to  three  secondary 


Mesonephros 

Diaphrag.  lig. 
of  mesonephros 

Pleural  cavity 

Bronchi 

Heart 


Aorta 

Upper  limb  bud 
(Esophagus 

Body  cavity 
Pericardial  cavity 


FIG.  324. — Transverse  section  of  a  14  mm.  pig  embryo,  at  the  level  of  the  upper  limb  buds, 
showing  especially  the  two  bronchi. 


buds,  the  forerunners  of  the  three  lobes  of  the  right  lung.  The  left  bud  gives 
rise  to  two  secondary  buds,  the  forerunners  of  the  two  lobes  of  the  left  lung 
(Fig.  325).  The  primary  buds  may  be  said  to  represent  the  two  bronchi  arising 
from  the  trachea,  the  five  secondary  buds  to  represent  the  bronchial  rami 
which  extend  into  the  five  lobes  of  the  lungs.  Successive  evaginations  from 
each  of  the  five  buds  take  place  and  form  an  extensive  arborization  for  each 
lobe  (Figs.  326  and  327). 


THE   DEVELOPMENT   OF  THE   RESPIRATORY  SYSTEM. 


367 


The  manner  in  which  the  bronchial  rami  branch  is  not  definitely  known. 
Some  maintain  that  the  branching  is  dichotomous,  that  is,  each  bud  gives  rise 
to  two  equal  buds  and  each  of  these  to  two  others,  and  so  on.  In  order  to  as- 
sume the  adult  form,  however,  one  of  the  buds  places  itself  in  line  with  the 
preceding  bud  or  bronchus  while  the  other  places  itself  as  a  lateral  outgrowth. 
Others  hold  that  the  growth  is  monopodial,  that  is,  that  the  original  bud  grows 
in  a  more  or  less  direct  line  and  the  others  develop  as  lateral  outgrowths.  When 


Upper  right  lobe 


Middle  right  lobe 


Trachea 


Upper  left  lobe 


Mesoderm 
(mesenchyme) 


Lower  right  lobe 

FIG.  325. — Anlage  of  lungs  of  a  human  embryo  of  4.3  mm.     His. 

the  evaginations  that  produce  the  bronchial  rami  are  completed,  each  terminal 
(respiratory)  bronchus  subdivides  into  three  to  six  narrow  tubules,  the  alveolar 
ducts.  The  latter  again  branch  into  several  wider  compartments,  the  atria, 
from  which  several  air  sacs  are  given  off.  The  walls  of  the  air  sacs  are  evagi- 
nated  to  form  many  closely  set  air  cells  which  represent  the  ultimate  branches 
of  the  air  passages  of  the  lungs. 


Trachea 


Right  bronchus 


Left  bronchus 


Bronchial  ramus 


Mesoderm 

(mesenchyme) 

Bronchial  ramus' 

FIG.  326. — Anlage  of  lungs  of  a  human  embryo  of  8.5  mm.     His. 

While  there  is  a  general  tendency  toward  bilateral  symmetry  in  the  various 
sets  of  bronchial  rami,  the  lobes  of  the  lungs  are  asymmetrical.  This  asym- 
metry is  indicated  in  the  five  secondary  buds  that  arise  from  the  two  primary, 
since  three  arise  on  the  right  side  and  only  two  on  the  left.  The  three  on  the 
right  represent  the  upper,  middle  and  lower  lobes  of  the  right  lung  (Fig.  325). 
The  upper  is  known  as  the  eparterial  from  the  fact  that  its  bronchus  lies  dorsal 


368 


TEXT-BOOK  OF  EMBRYOLOGY. 


to  the  pulmonary  artery.  No  lobe  develops  on  the  left  side  corresponding  to 
the  upper  (eparterial)  on  the  right.  There  is  a  possibility  that  it  is  absent  in 
order  to  allow  the  arch  of  the  aorta  to  migrate  caudally  as  it  normally  does 
(see  p.  247).  One  of  the  larger  ventral  bronchial  rami  of  the  left  lung  is  ab- 
sent, owing  to  the  inclination  of  the  heart  toward  the  left  side;  but  as  a  compensa- 
tion the  corresponding  ramus  of  the  right  lung  develops  more  extensively 
and  projects  into  the  space  between  the  pericardium  and  diaphragm  as  the 
infracardiac  ramus. 

From  the  fact  that  the  anlage  of  the  respiratory  system  is  enclosed  within 
the  mesentery  between  the  gut  and  the  pericardial  cavity,  and  that  its  caudal  end 
becomes  enclosed  within  the  dorsal  edge  of  the  septum  transversum,  it  is  obvious 


Pulmonary  artery 


Right  bronchus 


Upper  right 
bronch.  ramus 


Middle  right 
bronch.  ramus 


Lower  right 
bronch.  ramus 

Mesoderm 
(mesenchyme) 


—  Trachea 


Left  bronchus 


Upper  left 
bronch.  ramus 

Lower  left  branch 
oulmonary  vein 


Lower  left 
bronch.  ramus 


FIG.  327. — Anlage  of  lungs  of  a  human  embryo  of  10.5  mm.     His. 


that  the  lungs  will  push  their  way  into  the  dorsal  parietal  recesses  or  pleural 
cavities  (Figs.  328  and  333).  The  way  in  which  the  lungs  and  pleural  cavities 
enlarge  and  separate  the  pericardium  from  the  body  wall  on  each  side  and  from 
the  diaphragm  is  described  on  page  378  (see  Figs.  334  and  335).  The  mesoder- 
mal  tissue  that  surrounds  the  primary  lung  buds  is  in  part  pushed  before  the 
numerous  outgrowths  and  in  part  remains  among  them  (Figs.  325,  326,  327). 
The  part  around  the  lungs,  with  its  covering  of  mesothelium,  comes  to  form  the 
visceral  layer  of  the  pleura  which  closely  invests  the  entire  surface  of  the  lungs 
and  dips  down  between  the  lobes.  At  the  roots  of  the  lungs  it  is  continuous 
with  the  parietal  layer  of  the  pleura  lining  the  inner  surface  of  the  pleural  cavi- 
ties. The  mesodermal  tissue  among  the  bronchi  and  their  terminations  gives 
rise  to  the  connective  tissue  that  separates  the  lobes  and  lobules  and  invests  all 
the  structures  in  the  interior  of  the  lungs.  This  connective  tissue  at  first  con- 


THE   DEVELOPMENT   OF  THE   RESPIRATORY  SYSTEM. 


369 


stitutes  a  large  part  of  the  lungs,  but  as  development  proceeds,  the  more 
rapid  growth  of  the  respiratory  parts  results  in  the  relatively  small  amount  of 
connective  tissue  characteristic  of  the  adult  lung. 

Changes  in  the  Lungs  at  Birth. — At  birth  the  lungs  undergo  rapid  and 
remarkable  changes  in  consequence  of  their  assuming  the  respiratory  function. 
These  changes  affect  their  size,  form,  position,  texture,  weight,  etc.,  and 
furnish  probably  the  only  certain  means  of  distinguishing  between  a  still-born 
child  and  one  that  has  breathed.  In  the  foetus  at  term  the  lungs  are  small, 
possess  rather  sharp  margins  and  lie  in  the  dorsal  part  of  the  pleural  cavities. 


Diaphragm 


Lungs 


Pleural  cavities 


FIG.  328. — Transverse  section  of  a  pig  embryo  of  35  mm.,  showing  the  developing  lungs  (bronchial 
rami  surrounded  by  mesoderm).  The  oesophagus  is  seen  between  the  two  lungs;  above  the 
oesophagus  is  the  aorta.  The  dark  mass  in  the  lower  part  of  the  figure  is  the  liver. 
Photograph. 

After  respiration  they  enlarge,  fill  practically  the  entire  pleural  cavities  and 
naturally  become  more  rounded  at  their  margins.  The  introduction  of  air  into 
the  air  passages  converts  the  compact,  gland-like,  foetal  lung  into  a  loose, 
spongy  tissue.  The  specific  gravity  is  changed  from  1.056  to  0.342.  While 
there  is  a  gradual  increase  in  the  weight  of  the  lungs  during  development,  there 
is  a  very  sudden  increase  at  birth  when  the  blood  is  freely  admitted  to  them 
through  the  pulmonary  arteries.  The  weight  of  the  lungs  relative  to  that  of 
the  body  changes  from  about  i  to  70  before  birth,  to  about  i  to  35  or  40  after 
birth. 


TEXT-BOOK  OF  EMBRYOLOGY. 

Anomalies. 

THE  LARYNX. — The  larynx  may  be  excessively  large  or  unusually  small. 
Occasionally  the  epiglottic  cartilage  consists  of  two  pieces,  indicating  a  failure 
of  the  two  anlagen  to  fuse  (p.  364).  Similar  defects  may  occur  in  the  other 
cartilages  that  are  derived  from  more  than  one  anlage.  The  ventricle  on  either 
side  may  be  abnormally  large  with  an  exaggerated  appendage  (laryngeal 
pouch).  This  condition  resembles  that  in  the  anthropoid  apes. 

THE  TRACHEA. — The  trachea  is  sometimes  absent,  in  which  case  the  bronchi 
arise  immediately  below  the  larynx,  indicating  a  failure  on  the  part  of  the 
original  tube  to  elongate.  The  trachea  may  be  abnormally  short.  Rarely 
there  is  a  direct  communication  between  the  trachea  and  oesophagus,  probably 
due  to  an  incomplete  separation  of  the  lung  groove  from  the  gut  (p.  362).  The 
cartilaginous  rings  may  vary  in  number  as  a  result  of  abnormal  splittings  and 
fusions. 

THE  LUNGS. — Rarely  the  eparterial  bronchial  ramus  on  the  right  side 
arises  as  a  branch  of  the  trachea  and  not  as  a  branch  of  the  bronchus  (p.  367). 
This  condition  is  normal  in  certain  Mammals  (ox,  sheep).  Rarely  an  eparterial 
bronchial  ramus  is  present  on  the  left  side,  thus  producing  a  third  lobe  for 
the  left  lung.  In  some  animals  an  eparterial  ramus  is  normally  present  on 
each  side,  the  larger  bronchial  rami  thus  being  bilaterally  symmetrical.  Varia- 
tion in  size  and  number  of  lobes  is  not  infrequent.  Supernumerary  or  acces- 
sory lobes,  formed  either  by  evaginations  from  the  original  anlage  or  by  in- 
dependent evaginations  from  the  gut,  are  met  with  in  rare  cases. 

Occasionally  some  portion  of  either  lung  is  defective.  The  bronchial  bud 
that  would  normally  give  rise  to  the  lung  tissue  in  that  region  fails  to  develop 
properly,  and  the  result  is  a  number  of  rami,  without  the  ultimate  terminations, 
surrounded  by  vascular  tissue.  The  rami  may  remain  normal  or  may  become 
dilated  and  form  large  bronchial  cysts. 

PRACTICAL  SUGGESTIONS. 

The  anlage  of  the  respiratory  system  can  be  seen  in  chick  embryos  about  the  beginning 
of  the  third  day  of  incubation,  or  in  young  mammalian  embryos  (pig  embryos  of  6-8  mm.). 
Fix  in  Zenker's  fluid  or  in  Benin's  fluid,  cut  transverse  sections  in  the  cervical  region  and 
stain  with  Weigert's  haematoxylin  and  eosin.  Time  can  be  saved  by  staining  in  toto  with 
borax-carmin,  but  the  differentiation  is  not  so  good.  Either  technic  can  be  used  in  follow- 
ing succeeding  stages  of  development,  so  long  as  the  embryos  are  not  too  large  for  con- 
venience in  cutting  sections.  The  structure  and  relations  of  the  developing  pleura  can  also 
be  seen  in  these  sections.  In  fact  it  is  possible  to  use  the  same  sets  of  sections  for  the 
study  of  the  heart,  pericardium,  lungs  and  pleura. 

When  the  embryos  are  too  large  to  section  in  toto,  remove  the  lungs  and  subject  them 
to  the  above  technic.  Very  interesting  comparisons  can  be  made  between  sections  of  lung 
tissue  from  a  still-bom  child  and  from  one  which  has  breathed,  but  died  shortly  after. 


THE   DEVELOPMENT   OF  THE   RESPIRATORY  SYSTEM.  371 

References  for  Further  Study. 

BONNET,  R.:  Lehrbuch  der  Entwickelungsgeschichte.  Berlin,  1907. 

FLINT,  J.  M.:  The  Development  of  the  Lungs.     American  Jour,  of  Anat.,  Vol.  VI,  1906. 

GOPPERT,  E.:  Die  Entwickelung  des  Mundes  und  der  Mundhohle  mit  Driisen  und 
Zunge;  die  Entwickelung  der  Schwimmblase,  der  Lunge  und  des  Kehlkopfes  der  Wirbeltiere. 
In  Hertwig's  Handbuch  der  vergleich.  it.  experiment.  Entwickelungslehre  der  Wirbeltiere, 
Bd.  II,  Teil  I,  1902. 

HERTWIG,  O.:  Lehrbuch  der  Entwickelungsgeschichte  des  Menschen  und  der  Wirbel- 
tiere. Jena,  1906. 

His,  W.:  Zur  Bildungsgeschichte    der  Lungen  beim  menschlichen  Embryo.     Arch.  /. 
Anat.  u.  Physiol.,  Anat.  Abth.,  1887. 

KALLIUS,  E.:  Beitrage  zur  Entwickelungsgeschichte  des  Kehlkopfes.  Anal.  Hefte, 
Bd.  IX,  1897. 

KOLLMANN,  J.:  Lehrbuch  der  Entwickelungsgeschichte  des  Menschen.     Jena,  1898. 

KOLLMANN,  J.:  Handatlas  der  Entwickelungsgeschichte  des  Menschen.     Jena,  1907. 

McMuRRiCH,  J.  P.:  The  Development  of  the  Human  Body.     Third  Ed.,  1907. 

PIERSOL,  G.  A.:  Teratology.  In  Wood's  Reference  Handbook  of  the  Medical  Sciences, 
Vol.  VII,  1904. 

SYMINGTON,  J.:  On  the  Relations  of  Larynx  and  Trachea  to  the  Vertebral  Column  in 
the  Foetus  and  Child.  Journ.  of  Anat.  and  Physiol.,  Vol.  IX. 


CHAPTER  XIV. 

THE  DEVELOPMENT  OF  THE  CCELOM  (PERICARDIAL 

PLEURAL  AND  PERITONEAL  CAVITIES),  THE 

PERICARDIUM,  PLEUROPERITONEUM, 

DIAPHRAGM,  AND  MESENTERIES. 

In  the  Chapter  on  the  development  of  the  germ  layers,  it  is  stated  that  the 
peripheral  part  of  the  mesoderm  splits  into  two  layers,  an  outer  or  parietal,  and 
an  inner  or  visceral  (Fig.  81;  see  also  p.  87).  The  parietal  layer  of  mesoderm 
and  the  ectoderm  constitute  the  somatopleure.  The  visceral  layer  and  the 
entoderm  constitute  the  splanchnopleure  (Fig.  81).  The  cleft  or  cavity 
that  appears  between  the  parietal  and  visceral  layers  is  the  ccelom  or  body 
cavity  and  is  lined  with  a  layer  of  flattened  mesodermal  cells  known  as  the 
mesothelium.  It  will  be  remembered  that  in  the  earlier  stages  of  development  a 
portion  of  the  embryonic  disk  becomes  constricted  off  from  the  yolk  sac  to  form 
the  simple  cylindrical  body  (p.  141).  Along  each  side  of  the  axial  portion  of  the 
germ  disk,  and  also  at  its  cephalic  and  caudal  ends,  the  germ  layers  bend  ven- 
trally  and  then  medially  until  they  meet  and  fuse  in  the  midventral  line  (p.  141). 
In  this  way  a  part  of  the  somatopleure  forms  the  lateral  and  ventral  portions  of 
the  body  wall  (Fig.  141).  At  the  same  time  the  axial  portion  of  the  entoderm  is 
bent  into  a  tube  which  is  closed  at  both  ends — the  primitive  gut — and  is  then 
pinched  off  from  the  rest  of  the  entoderm  except  at  one  point,  where  the  cavity 
of  the  gut  remains  in  communication  with  the  cavity  of  the  yolk  sac.  The 
splanchnic  mesoderm  adjacent  to  the  entoderm  on  each  side  comes  in  contact 
and  fuses  with  the  corresponding  portion  from  the  opposite  side,  thus  forming 
a  sheet  of  tissue  which  encloses  the  primitive  gut  and  also  forms  a  partition  be- 
tween the  two  parts  of  the  ccelom.  This  sheet  of  tissue  is  the  common  mesentery 
and  is  attached  to  the  dorsal  and  ventral  body  walls  along  the  medial  line. 
The  portion  between  the  gut  and  the  dorsal  body  wall  is  the  dorsal  mesentery, 
the  portion  between  the  gut  and  the  ventral  body  wall  is  the  ventral  mesentery. 
Thus  the  gut  is  suspended  in  the  common  mesentery  (Figs.  235  and  320). 

When  portions  of  the  somatopleure  and  splanchnopleure  are  bent  ventrally 
the  ccelom  between  the  portions  is  naturally  carried  with  them.  This  part  of 
the  ccelom  thus  becomes  enclosed  within  the  cylindrical  body  and  constitutes 
the  intraembryonic  or  simply  the  embryonic  ccelom  (body  cavity  proper) .  The 
part  of  the  ccelom  which,  while  the  germ  layers  were  still  flat,  was  situated  more 
peripherally  constitutes  the  extraembryonic  ccelom  or  exocodom  (extraembryonic 

372 


PERICARDIUM,  PLEUROPERITONEUM,  DIAPHRAGM   AND  MESENTERIES.      373 

body  cavity).  From  the  nature  of  the  bending  process,  the  embryonic  coelom 
is  divided  into  bilaterally  symmetrical  parts  by  the  common  mesentery  (Fig. 
235).  These  two  simple  cavities  are  the  forerunners  of  all  the  serous  cavities  of 
the  body.  The  various  partitions  between  the  serous  cavities,  the  walls  of  the 
cavities  and  the  mesenteries  proper  are  all  derived  from  the  somatic  and 
splanchnic  mesoderm  with  its  covering  of  mesothelium. 

While  the  foregoing  would  represent  a  typical  case  of  early  ccelom  and 
mesentery  formation,  there  are  certain  modifications  and  peculiarities  in  the 
higher  Mammals  and  in  man.  In  all  cases  the  splitting  of  the  mesoderm  to 
form  the  ccelom  proceeds  from  the  periphery  of  the  germ  disk  toward  the  axial 
portion  (p.  89).  In  the  human  embryo  the  bending  ventrally  and  fusing  of  the 
germ  layers  to  form  the  cylindrical  body  begins  in  the  anterior  region  of  the 
disk  and  is  accomplished  there  before  the  splitting  of  the  mesoderm  is  com- 
pleted. The  peripheral  splitting  has  resulted  in  the  formation  of  the  exoccelom, 
but  at  the  time  when  the  ventral  fusion  of  the  germ  layers  takes  place,  the  split- 
ting has  not  extended  axially  to  a  sufficient  degree  to  form  the  intraembryonic 
coelom.  The  latter,  which  appears  later  in  this  region,  never  communicates 
laterally,  therefore,  with  the  exoccelom.  Caudal  to  this  region  the  ccelom  is 
formed  as  in  the  typical  case.  The  more  anterior  part  of  the  ccelom  on  each 
side  is  thus  primarily  a  pocket-like  cavity.  It  communicates  with  the  rest  of  the 
ccelom  at  about  the  level  of  the  yolk  stalk.  In  the  region  of  the  fore-gut,  the 
future  cesophagus,  no  distinct  mesentery  is  formed,  but  the  fore-gut  remains 
broadly  attached  to  the  dorsal  body  wall.  A  ventral  mesentery  is  lacking  from 
a  point  just  cranial  to  the  yolk  stalk  to  the  caudal  end  of  the  gut.  There  are 
no  ccelomic  cavities  in  the  branchial  arches,  the  ccelom  extending  only  to  the 
last  branchial  groove. 

In  very  young  human  embryos  the  primitive  segments  contain  small  cavities. 
These  cavities  soon  disappear,  being  filled  with  cells  from  the  surrounding 
parts  of  the  segments.  Whether  they  represent  isolated  portions  of  the  ccelom 
is  not  certain.  In  the  lower  Vertebrates,  the  cavities  of  the  primitive  segments 
regularly  communicate  with  the  ccelom,  and  in  the  sheep  the  cavities  of  the  first 
formed  segments  are  continuous  with  the  ccelom.  In  the  head  there  is  no 
cavity  analogous  to  the  ccelom  in  the  body.  In  but  one  human  embryo  have 
any  cavities  in  the  head  resembling  those  of  the  primitive  segments  been 
observed  (see  p.  301). 

The  Pericardial  Cavity,  Pleural  Cavities  and  Diaphragm. 

The  pericardial  and  pleural  cavities  and  diaphragm  are  so  closely  related  in 
their  development  that  they  must  be  considered  together.  In  the  region  just 
caudal  to  the  visceral  arches,  where  the  two  anlagen  of  the  heart  appear,  the 
embryonic  ccelom  becomes  dilated  at  a  very  early  stage  to  form  the  primitive 
pericardial  cavity  (parietal  cavity  of  His).  After  the  two  anlagen  of  the  heart 


374  TEXT-BOOK  OF  EMBRYOLOGY. 

unite  to  form  a  simple  tubular  structure  (p.  222;  also  Fig.  194),  the  latter  is 
suspended  in  the  cavity  by  a  mesentery  which  consists  of  a  dorsal  and  a  ventral 
part,  a  dorsal  and  a  ventral  mesocardium.  By  these  the  cavity  is  at  first  divided 
into  two  bilaterally  symmetrically  parts.  The  mesocardia  soon  disappear  and 
leave  the  heart  attached  only  to  the  large  vascular  trunks  which  suspend  it 
in  the  single  pericardial  cavity.  The  early  pericardial  cavity  is  simply  the 
cephalic  end  of  the  embryonic  ccelom  and  is  therefore  directly  continuous  with 
the  rest  of  the  ccelom.  As  mentioned  on  p.  373  it  does  not,  however,  at  any 
time  communicate  laterally  with  the  extraembryonic  ccelom. 

The  communication  between  the  pericardial  cavity  and  the  rest  of  the  em- 
bryonic ccelom  is  soon  partly  cut  off  by  the  development  of  a  transverse  fold 
— the  septum  transversum.  This  septum  is  formed  in  close  relation  with  the 
omphalomesenteric  veins.  These  vessels  unite  in  the  sinus  venosus  at  the 
caudal  end  of  the  heart,  whence  they  diverge  in  the  splanchnic  mesoderm. 


am 


vom 


FIG.  329. — Transverse  sections  of  a  rabbit  embryo,  showing  how  the  omphalomesenteric  veins  (vom) 
push  outward  across  the  ccelom  and  fuse  with  the  lateral  body  wall,  forming  the  ductus 
pleuro-pericardiacus  (rp,  rpd) ;  am,  amnion.  Ravn. 

They  are  thus  embedded  in  the  mesodermal  layer  of  the  splanchnopleure,  and  as 
the  latter  closes  in  from  either  side  to  form  the  gut,  the  vessels  form  ridge-like 
projections  into  the  ccelom.  As  the  vessels  increase  in  size,  the  ridges  become 
so  large  that  the  splanchnic  mesoderm  is  pushed  outward  against  the  parietal 
mesoderm  and  fuses  with  it  (Fig.  329).  Thus  a  partition  is  formed  on  each  side, 
which  is  attached  on  the  one  hand  to  the  mesentery  and  on  the  other  hand  to  the 
ventral  and  lateral  body  walls,  and  which  contains  the  omphalomesenteric  veins. 
It  is  obvious  that  these  partitions,  forming  the  septum  transversum,  close  the 
ventral  part  of  the  communication  between  the  pericardial  cavity  and  the  rest  of 
the  ccelom.  The  dorsal  part  of  the  communication  remains  open  on  each  side 
of  the  mesentery  as  the  ductus  pleuro-pericardiacus  (dorsal  parietal  recess  of  His) 
(Figs.  329  and  330). 

As  the  heart  develops  it  migrates  caudally,  and  by  corresponding  migration 
the  pericardial  cavity  draws  the  ventral  edge  of  the  septum  transversum  farther 
caudally,  so  that  the  cephalic  surface  of  the  latter  faces  ventrally  and  cranially. 


PERICARDIUM,  PLEUROPERITONEUM,  DIAPHRAGM  AND  MESENTERIES.      375 

In  other  words  the  septum  comes  to  lie  in  an  oblique  cranio-caudal  plane.  The 
pericardial  cavity  therefore  comes  to  lie  ventral  to  the  ductus  pleuro-pericardiaci. 
The  latter— one  on  each  side  of  the  mesentery— are  two  passages  which  com- 


Pericardial  cavity 

Lateral  mesocardium 

Pericardium 

Septum  transversum 

Liver 

Ductus  choledochus 


Yolk  s 


Ventral  aortic  trunk 
Dorsal  mesocardium 

Sinus  venosus 
Duct  of  Cuvier 

Left  umbilical  vein 
Left  omphalomes.  vein 
Ductus  pleuro-pericardiacus 

Stomach 
Peritoneal  cavity 


FIG.  330. — From  a  model  of  the  septum  transversum,  liver  etc.,  of  a  human  embryo 
of  3  mm.     His,  Kollman. 

municate  on  the  one  hand  with  the  pericardial  cavity  and  on  the  other  hand  with 
the  peritoneal  cavity,  while  they  themselves  form  the  cavities  into  which  the  lungs 
grow — the  pleural  cavities,  (Compare  Figs.  330,  331  and  332.) 


Pharynx 
Dorsal  mesocardium 


Ductus  pleuro- 
pericardiacus 


Aorta 


.Ductus  pleuro- 
pericardiacus 
Duct  of  Cuvier 


Heart 


Pericardial  cavity 

FIG.  331. — View  (in  perspective)  of  the  pericardial  cavity  and  ductus  pleuro-pericardiaci 
of  a  rabbit  embryo  of  9  days.     Ravn. 

The  pleural  cavities  also  become  separated  from  the  pericardial  cavity,  ap- 
parently through  the  agency  of  the  ducts  of  Cuvier.  The  anterior  and  posterior 
cardinal  veins  on  each  side  unite  to  form  the  duct  of  Cuvier  which  then  extends 


376 


TEXT-BOOK  OF  EMBRYOLOGY. 


from  the  body  wall  through  the  dorsal  free  edge  of  the  septum  transversum  to 
join  the  sinus  venosus  (Fig.  330).  This  free  edge  is  pushed  farther  and 
farther  into  the  ductus  pleuro-pericardiacus  (Fig.  331)  until  it  meets  and  fuses 


Pleural  cavity 


\ 


Dorsal  mesentery 


Lung. 


Lateral  mesocardium  —  ft- 


Pericardial  cavity  -*" 


Lateral  mesocardium 


1  Dorsal  mesocardium 
Heart 


FIG.  332. — View  (in  perspective)  of  the  pericardial  and  pleural  cavities  of  a  human  embryo 

of  7.5  mm.     Kollmann. 

The  arrow  points  through  the  opening  which  forms  the  communication  between  the  pleural 
and  peritoneal  cavities,  and  which  is  eventually  closed  by  the  pleuro- peritoneal  membrane. 

with  the  mesentery  or  posterior  mediastinum.     This  process  thus  produces  a 
septum  between  each  pleural  cavity  and  the  pericardial  cavity. 

The  septum  transversum  early  acquires  still  more  complicated  relations 


Pleuro-peritoneal  membrane 


Mesentery  of 
inf.  vena  cava 


Inferior  vena  cava  : * 

Mesonephros  V-t 

V 


Pleuro-peritoneal  membrane 
--^Mesentery 

P1  euro-peritoneal  membrane 
CEsophagus 


•-.'-•(  Dorsal  mesogastrium 


FIG.  333. — Ventral  view  (in  perspective)  of  parts  of  the  lungs,  pleural  cavities,  peritoneal  cavity, 
and  the  pleuro-peritoneal  membranes  in  a  rat  embryo.     Ravn. 

from  the  fact  that  the  liver  grows  into  its  caudal  part  (Fig.  330) .  It  may,  for  this 
reason,  be  divided  into  a  caudal  part  in  which  the  liver  is  situated  and  wrhich 
furnishes  the  fibrous  capsule  (of  Glisson)  and  the  connective  tissue  of  the  liver, 
and  a  cephalic  part  which  may  be  called  the  primary  diaphragm.  These  two 
parts  at  first  are  not  separate,  the  separation  taking  place  secondarily.  After 


PERICARDIUM,  PLEUROPERITONEUM,  DIAPHRAGM  AND  MESENTERIES.      377 


the  separation  between  the  pericardial  cavity  and  the  pleural  cavities,  the  latter 
for  a  time  remain  in  open  communication  with  the  rest  of  the  ccelom  or  peritoneal 
cavity.  The  lungs,  as  they  develop,  grow  into  the  pleural  cavities  (Fig.  332) 
until  their  tips  finally  touch  the  cephalic  surface  of  the  liver.  At  this  point 
folds  grow  from  the  lateral  and  dorsal  body  walls  (Fig.  333)  and  unite  ventrally 
with  the  primary  diaphragm  and  medially  with  the  mesentery.  These  folds — 
the  pleuroperitoneal  membranes — separate  the  pleural  cavities  from  the  perit- 
oneal cavity  and  complete  the  diaphragm.  Thus  the  diaphragm,  from  the  stand- 


Lv.c. 


FIG.  335. 

FIG.  334. — Transverse  section  through  the  thoracic  region  of  a  rabbit  embryo  of  15  days.  Hochstetter. 
FlG.  335. — Transverse  section  through  the  thoracic  region  of  a  cat  embryo  of  25  mm.  Hochstetter. 
I.v.c..  Inferior  vena  cava;  Inf.-c.  1.,  infracardiac  lobe  of  lung;  L.,  lung;  Oe..  cesophagus;  Pc.cav., 

pericardial  cavity;  PI.  cav.,  pleural  cavity;  Pl.-p.  m.,  pleuro-pericardial  membrane;  Pu.-h.  r., 

pulmo-hepatic  recess. 

point  of  development,  consists  of  two  parts :  a  ventral  part  which  is  the  cephalic 
portion  of  the  original  septum  transversum,  and  a  dorsal  part  which  develops 
later  from  the  body  wall  and  is  the  closing  membrane  between  the  peritoneal 
and  pleural  cavities.  The  musculature  of  the  diaphragm  is  considered  in  the 
chapter  on  the  muscular  system  (p.  300). 

While  the  foregoing  structures  are  being  formed,  decided  changes  take  place 
in  their  positions  and  delations.  At  first  the  heart  lies  far  forward  in  the  cervi- 
cal region  near  the  visceral  arches.  Later  it  migrates  caudally  and  the  pericardial 


378 


TEXT-BOOK  OF  EMBRYOLOGY. 


cavity  comes  to  occupy  much  of  the  ventral  part  of  the  thorax,  the  pericardium 
having  extensive  attachments  to  the  ventral  body  wall  and  to  the  cephalic  sur- 
face of  the  primary  diaphragm  (Fig.  330).  The  diaphragm  is  much  farther 
forward  than  in  the  adult  and  is  broadly  attached  to  the  cephalic  surface  of  the 
liver.  The  principal  changes  which  bring  about  the  adult  conditions  are  the 
growth  of  the  lungs,  the  separation  of  the  diaphragm  from  the  liver,  and  the 

caudal  migration  of  the  diaphragm  itself.  With 
the  development  of  the  lungs,  the  pleural  cavities 
necessarily  enlarge  and  push  their  way  ventrally. 
In  so  doing  they  split  the  pericardium  away  from 
the  lateral  body  walls  and  likewise  from  the  dia- 
phragm (compare  Figs.  334  and  335).  Thus  the 
pericardial  cavity  comes  to  be  confined  more  and 
more  closely  to  the  medial  ventral  position.  The 
separation  of  the  liver  from  the  primary  diaphragm 
is  caused  by  changes  in  the  peritoneum  which  at 
first  covers  the  caudal,  lateral  and  ventral  surfaces 
of  the  liver.  The  cephalic  surface  of  the  liver,  as 
stated  above,  is  covered  by  the  primary  diaphragm 
itself.  The  peritoneum  is  reflected  from  the  surface 
of  the  liver  on  to  the  diaphragm,  and  at  the  line  of 
reflection  a  groove  appears  on  each  side,  extending 
from  the  midventral  line  around  as  far  as  the 
attachment  of  the  liver  to  the  diaphragm.  The 
—Diagram  showing  the  grooves  gradually  grow  deeper,  the  peritoneum 
P»>*ing  i*  way,  as  a  flat  sac,  between  the  two 
stages.  Mall.  structures,  until  the  separation  is  almost  complete. 

The   positions  are  those  shown  . 

in  embryos  of  Mall's  collection    There   is    left,    however,    an   area  of  attachment 
(except  KO,  which  is  a  10.2    between  the  liver  and  diaphragm,  over  which  the 

mm.  embryo  of  the  His  collec- 

tion); XII  being  an  embryo  of    peritoneum  is  reflected,  the  ligamentum  coronarium 


FIG 


IX,  of  17  mm.;  XLIII,  of  15 

mm.;   VI,  of  24  mm.      The 

numerals  on  the  right  indicate    phragm,  the  liver  and  the  ventral  body  wall. 


hepatis.     In  the  medial  line  there  is   also   left  a 
broad  thin  lamella  which  is  attached  to  the  dia- 

. 
This 

is  a  remnant  of  the  ventral  mesentery  and  forms 
the  ligamentum  suspensorium  (falciforme)  hepatis.  In  its  free  caudal  edge 
is  embedded  the  ligamentum  teres  hepatis  which  is  closely  related  to  the 
umbilical  vein  (see  p.  265).  The  diaphragm  itself,  during  its  development, 
migrates  from  a  position  in  the  cervical  region,  where  the  septum  transversum 
first  appears,  to  its  final  position  opposite  the  last  thoracic  vertebrae.  During 
the  migration  the  plane  of  direction  also  changes  several  times,  as  may  be 
seen  in  Fig.  336. 


PERICARDIUM,  PLEUROPERITONEUM,  DIAPHRAGM   AND  MESENTERIES.      379 

The  Pericardium  and  Pleura.— Since  the  pericardial  cavity  represents  a 
portion  of  the  original  ccelom,  the  lining  of  the  cavity  must  be  a  derivative  of 
either  the  parietal  or  the  visceral  layer  of  mesoderm  or  of  both.  The  common 
mesentery  in  which  the  heart  develops  is  derived  from  the  visceral  layer.  Con- 
sequently the  epicardium  is  a  derivative  of  the  visceral  mesoderm  (Fig.  194). 
The  pericardium  is  derived  from  three  regions  of  mesoderm.  The  greater 
part  is  derived  from  the  parietal  mesoderm,  since  the  body  wall  which  is  com- 
posed of  parietal  mesoderm  is  also  primarily  the  wall  of  the  pericardial  cavity. 
A  small  dorsal  portion  is  probably  derived  from  the  mesoderm  at  the  root  of  the 
dorsal  mesocardium  (Fig.  194).  The  septum  transversum  primarily  forms 
the  caudal  wall  of  the  pericardial  cavity,  and,  since  the  septum  is  a  derivative 
of  the  visceral  layer,  the  caudal  wall  is  derived  from  this  layer.  The  three 
portions  are,  of  course,  continuous. 

The  lungs  first  appear  in  the  common  mesentery  as  an  evagination  from  the 
primitive  gut  (Fig.  320,  p.  362).  As  they  develop  further  they  grow  into  the 
pleural  cavities,  pushing  a  part  of  the  mesentery  before  them.  This  part  of 
the  mesentery  thus  invests  the  lungs  and  forms  the  visceral  layer  of  the  pleura 
which  is  therefore  a  derivative  of  the  visceral  mesoderm.  The  parietal  layer  of 
the  pleura  is  a  derivative  of  the  parietal  mesoderm,  since  the  wall  of  the  pleural 
cavity  is  primarily  the  body  wall. 

The  lining  of  all  these  cavities  is  at  first  composed  of  mesothelium  and 
mesenchyme.  The  latter  is  transformed  into  the  delicate  connective  tissue  of 
the  serous  membranes,  and  the  mesothelium  becomes  the  mesothelium  of 
the  membranes. 

The  Omentum  and  Mesentery. 

From  the  septum  transversum  (or  diaphragm)  to  the  anus  the  gut  is  sus- 
pended in  the  ccelom  (or  abdominal  cavity)  by  means  of  the  dorsal  mesentery. 
This  is  attached  to  the  dorsal  body  wall  along  the  medial  line  and  lies  in  the 
medial  sagittal  plane  (Fig.  301;  compare  with  Fig.  235).  On  the  ventral  side  of 
the  gut  a  mesentery  is  lacking  from  the  anus  to  a  point  just  cranial  to  the  yolk 
stalk  (p.  373).  There  is,  however,  a  small  ventral  mesentery  extending  a  short 
distance  caudally  from  the  septum  transversum.  On  account  of  its  relation  to 
the  stomach  this  is  known  as  the  ventral  mesogastrium  (Fig.  301).  These  two 
sheets  of  tissue,  the  dorsal  and  ventral  mesenteries,  are  destined  to  give  rise  to 
the  omenta  and  mesenteries  of  the  adult.  Owing  to  the  enormous  elongation  of 
the  gut  and  its  extensive  coiling  in  the  abdominal  cavity,  the  primary  mesen- 
teries are  twisted  and  thrown  into  many  folds  which  enclose  certain  pockets  or 
bursae.  Furthermore,  certain  parts  of  the  gut  which  are  originally  free  and 
movable  become  attached  to  other  parts  and  to  the  body  walls  through  fusions 
of  certain  parts  of  the  mesentery  with  one  another  and  with  the  body  walls. 


380 


TEXT-BOOK  OF  EMBRYOLOGY. 


The  Greater  Omentum  and  Omental  Bursa. — A  small  part  of  the  gut 
caudal  to  the  diaphragm  is  destined  to  become  the  stomach,  and  the  portion  of 
the  mesentery  which  attaches  it  to  the  dorsal  body  wall  is  known  as  the  dorsal 
mesogastrium  (Fig.  301).  The  latter  is  inserted  along  the  greater  curvature  of 
the  stomach  and  lies  in  the  medial  sagittal  plane  so  long  as  the  stomach  lies  in 
this  plane.  When  the  stomach  turns  so  that  its  long  axis  lies  in  a  transverse 
direction  and  its  greater  curvature  is  directed  caudally  (p.  337),  the  dorsal 
mesogastrium  changes  its  position  accordingly.  From  its  attachment  along  the 
dorsal  body  wall  it  bends  to  the  left  and  then  ventrally  to  its  attachment  along 
the  greater  curvature  of  the  stomach.  Thus  a  sort  of  sac  is  formed  dorsal  to 
the  stomach  (Figs.  337  and  338).  This  sac  is  really  a  part  of  the  abdominal  or 


Stomach 


Stomach 


Duodenum 


Yolk  stalk 


Rectum 


Caecum1 
Appendix 
Mesentery 

Yolk  stalk 


Rectum 


FIG.  337. 


FIG.  338. 

FIG.  337. — Diagram  of  the  gastrointestinal  tract  and  its  mesenteries 

at  an  early  stage.     Ventral  view.     Hertwig. 
FIG.  338. — Same  at  a  later  stage :     Hertwig, 
The  arrow  points  into  the  bursa  omentalis. 


peritoneal  cavity  and  opens  toward  the  right  side.  The  ventral  wall  is  formed 
by  the  stomach,  the  dorsal  and  caudal  walls  by  the  mesogastrium.  The  cavity 
of  the  sac  is  the  omental  bursa  (bursa  omentalis) ;  the  mesogastrium  forms  the 
greater  amentum  (omentum  ma  jus) .  The  opening  from  the  bursa  into  the  general 
peritoneal  cavity  is  the  epiploic  foramen  (foramen  of  Winslow).  (Fig.  314.) 

From  the  third  month  on,  the  greater  omentum  becomes  larger  and  gradually 
extends  toward  the  ventral  abdominal  wall,  over  the  transverse  colon,  and  then 
caudally  between  the  body  wall  and  the  small  intestine  (Figs.  339  and  340). 
The  portion  between  the  body  wall  and  intestine  encloses  merely  a  flat  cavity 
continuous  with  the  larger  cavity  dorsal  to  the  stomach.  From  the  fourth 
month  on,  the  omentum  fuses  with  certain  other  structures  and  becomes  less 
free.  The  dorsal  lamella  fuses  with  the  dorsal  body  wall  on  the  left  side  and 


PERICARDIUM,  PLEUROPERITONEUM,  DIAPHRAGM   AND   MESENTERIES.      381 

with  the  transverse  mesocolon  and  transverse  colon  (Fig.  341).  During  the 
first  or  second  year  after  birth  the  two  lamellae  fuse  with  each  other  caudal 
to  the  transverse  colon  to  form  the  greater  omentum  of  adult  anatomy. 


Diaphragm. 

Liver-. __ 
Lesser  omentum. __ 

Pancreas--,^ 
Bursa  omentalis 

Stomach 

Greater  omentum 

Duodenum 

Transverse  mesocolon  - 
Transverse  colon  -  -Vi, 


Mesentery  of 
small  intestine  " 


Small  intestine 


FIG.  339. 


Diaph. 


FIG.  340.  FIG.  341. 

IGS.  339,  340  and  341. — Diagrams  showing  stages  in  the  development  of  the  bursa  omentalis,  the 
greater  omentum,  and  the  fusion  of  the  latter  with  the  transverse  mesocolon.  Diagrams 
represent  sagittal  sections.  For  explanation  of  lettering  in  Figs.  340  and  341  see  Fig.  339. 

The  Lesser  Omentum. — It  has  already  been  noted  that  the  liver  grows  into 
ie  caudal  portion  of  the  septum  transversum  (p.  376).  Since  the  ventral 
lesentery  in  the  abdominal  region,  or  the  ventral  mesogastrium,  is  primarily 


382  TEXT-BOOK  OF  EMBRYOLOGY. 

directly  continuous  with  the  septum  transversum,  it  is  later  attached  to  the 
liver.  In  other  words  it  passes  between  the  liver  and  the  lesser  curvature  of  the 
stomach  and  also  extends  along  the  duodenal  portion  of  the  gut  for  a  short 
distance  (Fig.  301).  As  the  stomach  turns  to  the  left  the  ventral  mesentery  is 
also  drawn  toward  the  left  and  comes  to  lie  almost  at  right  angles  to  the  sagittal 
plane  of  the  body,  forming  the  lesser  amentum  (omentum  minus)  or  the  hepato- 
gastric  and  hepatoduodenal  ligaments  of  the  adult  (Figs.  341  and  342). 

The  Mesenteries. — So  long  as  the  intestine  is  a  straight  tube,  the  dorsal 
mesentery  lies  in  the  medial  sagittal  plane,  its  dorsal  attachment  being  practi- 
cally of  the  same  length  as  its  ventral  (intestinal)  attachment.  As  development 
proceeds,  the  intestine  elongates  much  more  rapidly  than  the  abdominal  walls, 
and  the  intestinal  attachment  of  the  mesentery  elongates  accordingly.  When 
the  portion  of  the  intestine  to  which  the  yolk  stalk  is  attached  grows  out  into  the 
proximal  end  of  the  umbilical  cord  (p.  339),  the  corresponding  portion  of  the 
mesentery  is  drawn  out  with  it  (Fig.  301).  When  the  intestine  returns  to  the 
abdominal  cavity  and  forms  the  primary  loop,  with  the  caecum  to  the  right  side 
(p.  340),  its  mesenteric  attachment  is  carried  out  of  the  medial  sagittal  plane. 
This  results  in  a  funnel-shaped  twisting  of  the  mesentery  (Figs.  337  and  338). 
The  portion  of  the  mesentery  which  forms  the  funnel  is  destined  to  become  the 
mesentery  of  the  jejunum,  ileum,  and  ascending  and  transverse  colon,  and  is 
attached  to  the  dorsal  body  wall  at  the  apex  of  the  funnel  (Fig.  337,  338,  342). 
This  condition  is  reached  about  the  middle  of  the  fourth  month. 

Up  to  this  time  the  mesentery  and  intestine  are  freely  movable,  that  is,  they 
have  formed  no  secondary  attachments.  From  this  time  on,  as  the  intestine 
continues  to  elongate  and  forms  loops  and  coils,  the  mesentery  is  thrown  into 
folds,  and  certain  parts  of  it  fuse  with  other  parts  and  with  the  body  wall. 
Thus  certain  parts  of  the  intestine  become  less  free  or  less  movable  within  the 
abdominal  cavity. 

The  duodenum  changes  from  the  original  longitudinal  position  to  a  more 
nearly  transverse  position  and,  with  its  mesentery — the  mesoduodenum — fuses 
with  the  dorsal  body  wall,  thus  becoming  firmly  fixed.  Since  the  mesoduode- 
num fuses  with  the  body  wall,  the  duodenum  has  no  mesentery  in  the  adult. 
The  pancreas,  which  is  primarily  enclosed  within  the  mesoduodenum,  also 
becomes  firmly  attached  to  the  dorsal  body  wall  (compare  Figs.  339  and  340). 

The  mesentery  of  the  transverse  colon,  or  the  transverse  mesocolon,  which 
lies  across  the  body  ventral  to  the  duodenum  (Figs.  338  and  342),  fuses  with  the 
ventral  surface  of  the  latter  and  with  the  peritoneum  of  the  dorsal  body  wall. 
In  this  way  the  dorsal  attachment  of  the  transverse  mesocolon  is  changed  from 
its  original  sagittal  direction  to  a  transverse  direction  (Figs.  340  and  341).  The 
mesocolon  itself  forms  a  transverse  partition  which  divides  the  peritoneal  cavity 
into  two  parts,  an  upper  (or  cranial)  which  contains  the  stomach  and  liver,  and 


PERICARDIUM,  PLEUROPERITONEUM,  DIAPHRAGM   AND   MESENTERIES.      383 

a  lower  (or  caudal)  which  contains  the  rest  of  the  digestive  tube  except  the 
duodenum.  The  mesentery  of  the  duodenum  and  pancreas  changes  from  a 
serous  membrane  into  subserous  connective  tissue,  and  these  two  organs  as- 
sume the  retroperitoneal  position  characteristic  of  the  adult  (Fig.  339). 

The  mesentery  of  the  descending  colon,  or  the  descending  mesocolon,  lies  in 
the  left  side  of  the  abdominal  cavity,  in  contact  with  the  peritoneum  of  the  body 
wall  (see  Fig.  342).  It  usually  fuses  with  the  peritoneum,  and  the  descending 


Dors,  mesogastrium 


Lesser  omentum 
(hep.-gast.  lig.) 


Bile  duct 


Mesoduodenum        


Transv.  colon 


Spleen 


Duo.-jej.  flexure 

Desc.  colon 
Desc.  mesocolon 


Appendix 


Yolk  stalk 


Medial  line 

FIG.  342. — Gastrointestinal  tract  and  mesenteries  in  a  human  embryo.     The  arrow 
points  into  the  bursa  omentalis.     Kollmann. 


colon  thus  becomes  fixed.  After  the  ascending  colon  is  formed,  the  ascending 
mesocolon  usually  fuses  with  the  peritoneum  on  the  right  side  (see  Fig.  342).  In 
a  large  percentage  (possibly  25  per  cent.)  of  individuals,  the  fusion  between  the 
peritoneum  and  the  ascending  and  descending  mesocolon  is  incomplete  or 
wanting. 

The  sigmoid  mesocolon  bends  to  the  left  to  reach  the  sigmoid  colon,  but 
forms  no  secondary  attachments.  It  is  continuous  with  the  mesorectum  which 
maintains  its  original  sagittal  position.  A  sheet  of  tissue — the  mesoappendix — 
continuous  with  and  resembling  the  mesentery,  is  attached  to  the  caecum  and 
vermiform  appendix  (Fig.  342) .  It  probably  represents  a  drawn  out  portion  of 
25 


384  TEXT-BOOK  OF  EMBRYOLOGY. 

the  original  common  mesentery,  since  the  cascum  and  appendix  together  are 
formed  as  an  evagination  from  the  primitive  gut. 

Normally  the  mesentery  of  the  small  intestine  forms  no  secondary  attach- 
ments, but  is  thrown  into  a  number  of  folds  which  correspond  to  the  coils  of  the 
intestine. 

The  secondary  attachments  of  the  greater  omentum  and  the  fusion  of  the 
two  lamellae  have  been  described  earlier  in  this  chapter  (p.  380).  The  mesen- 
teries of  the  urogenital  organs  are  considered  in  connection  with  the  develop- 
ment of  those  organs  (Chapter  XV). 

The  Peritoneum. — The  thin  layer  of  tissue — composed  of  delicate  fibrous 
connective  tissue  and  mesothelium — which  lines  the  abdominal  cavity  and  is  re- 
flected over  the  various  omenta,  mesenteries  and  visceral  organs,  is  derived 
wholly  from  the  mesoderm.  The  lining  of  the  ccelom  is  composed  of  mesothe- 
lium and  mesenchyme.  The  latter  gives  rise  to  the  connective  tissue  of  the 
serous  membranes,  and  the  mesothelial  layer  becomes  the  mesothelium  of  these 
membranes. 

Anomalies. 

THE  PERICARDIUM. — Anomalous  conditions  of  the  pericardium  are  usually, 
although  not  necessarily,  associated  with  anomalies  of  the  heart.  They  may 
also  be  associated  with  defects  in  the  diaphragm.  Displacement  of  the  heart 
(ectopia  cordis)  is  accompanied  by  displacement  of  the  pericardium.  The 
heart  sometimes  protrudes  through  the  thoracic  wall,  and,  as  a  rule,  in  such  cases 
is  covered  by  the  protruding  pericardium.  In  extensive  cleft  of  the  thoracic 
wall  (thoracoschisis,  Chap.  XIX)  the  pericardium  may  be  ruptured. 

THE  DIAPHRAGM. — The  most  common  malformation  of  the  diaphragm  is  a 
defect  in  its  dorsal  part,  occurring  much  more  frequently  on  the  left  than  on  the 
right  side.  The  defect  may  affect  but  a  small  portion  or  may  be  extensive,  the 
peritoneum  being  directly  continuous  with  the  parietal  layer  of  the  pleura. 
Such  defects  are  due  to  the  imperfect  development  of  the  pleuro-peritoneal  mem- 
brane which  normally  grows  from  the  dorso-lateral  part  of  the  body  wall  and 
fuses  with  the  edge  of  the  primary  diaphragm,  thus  separating  the  pleural  and 
and  peritoneal  cavities  (p.  377).  The  most  conspicuous  result  of  defects  in  the 
dorsal  part  of  the  diaphragm  is  diaphragmatic  hernia,  in  which  parts  of  the 
stomach,  liver,  spleen  and  intestine  project  into  the  pleural  cavity,  either  free  or 
enclosed  in  a  peritoneal  sac.  Defects  in  the  ventral  part  of  the  diaphragm,  due 
to  imperfect  development  of  portions  of  the  septum  transversum,  are  not 
common. 

THE  MESENTERIES  AND  OMENTA. — Extensive  malformations  of  the  mesen- 
teries apparently  do  not  occur  without  extensive  malformations  of  the  digestive 
tract.  One  of  the  most  striking  anomalous  conditions  is  a  retained  embryonic 


PERICARDIUM,  PLEUROPERITONEUM,  DIAPHRAGM  AND  MESENTERIES.      385 

simplicity  of  the  mesentery,  concurrent  with  corresponding  simplicity  in  the 
loops  and  coils  of  the  intestine.  In  this  anomaly  the  intestine  has  failed  to 
arrive  at  its  usual  complicated  condition  and  the  mesentery  has  not  undergone 
the  usual  processes  of  folding  and  fusion  (p.  382  et  seq.}.  Minor  variations  in 
the  mesenteries  and  omenta  are  probably  due  largely  to  imperfect  fusion  of 
certain  parts  with  one  another  and  with  the  body  wall.  It  is  not  uncommon  to 
find  the  ascending  or  descending  colon,  or  both,  more  or  less  free  and  mov- 
able. This  condition  is  due  to  imperfect  fusion  of  the  mesocolon  with  the  body 
wall  (p.  383).  If  the  greater  omentum  is  wholly  or  partially  divided  into  sheets 
of  tissue,  the  two  primary  lamellae  have  failed  to  fuse  completely  (p.  381). 
This  divided  condition  is  normal  in  many  Mammals. 

PRACTICAL  SUGGESTIONS. 

The  Ccelom  and  Common  Mesentery. — Chick  embryos  afford  excellent  material  for  the 
study  of  the  formation  of  the  ccelom  and  common  mesentery.  Use  successive  stages  during 
the  latter  part  of  the  first  day  and  during  the  second  day  of  incubation.  Remove  the 
embryo  from  the  egg,  being  careful  to  keep  it  as  nearly  as  possible  in  the  natural  position, 
fix  in  Flemming's  or  in  Zenker's  fluid,  cut  transversely  in  paraffin  and  stain  with  Heidenhain's 
haematoxylin.  Time  can  be  saved  by  staining  in  Mo  in  borax  carmin,  but  the  differentia- 
tion is  not  so  clear.  The  various  stages  in  the  development  of  the  coelom  and  mesentery 
are  well  shown.  If  serial  sections  are  cut,  one  can  often  trace  the  successive  stages  in  one 
embryo  by  examining  sections  in  succession  through  the  series,  for  the  bending  of  the  germ 
layers  begins  in  the  head  region  and  gradually  progresses  toward  the  tail. 

The  Primitive  Pericardial  Cavity. — The  dilatation  of  the  ccelom  in  the  cervical  region  to 
form  the  primitive  pericardia!  cavity  can  be  seen  in  transverse  sections  of  chick  embryos  of 
the  latter  part  of  the  first  day  of  incubation.  Prepare  the  specimens  as  directed  in  the  pre- 
ceding paragraph.  The  specimens  prepared  for  the  study  of  the  ccelom  and  mesentery 
will  serve  this  purpose  if  sections  from  the  cervical  region  are  selected. 

The  Septum  Transversum. — The  early  stages  of  the  septum  can  be  seen  in  sections  of 
chick  embryos  of  the  second  day  of  incubation,  prepared  as  directed  above.  It  is  best  to  cut 
serial  sections.  By  tracing  the  omphalomesenteric  veins,  the  ridges  formed  by  the  veins 
can  be  seen  projecting  into  the  ccelom.  If  later  stages  are  examined,  the  ridges  will  be  seen 
to  extend  across  the  ccelom  and  to  fuse  with  the  ventro -lateral  part  of  the  body  wall.  The 
ridges  form  the  anlage  of  the  septum. 

Later  Stages. — The  study  of  the  later  stages  becomes  more  difficult  as  the  structures 
increase  in  complexity.  Chick  or  mammalian  embryos  in  different  stages  are  fixed  in 
Zenker's  fluid  or  Bouin's  fluid,  sectioned  transversely  in  paraffin,  and  stained  with  Weigert's 
haematoxylin  and  eosin.  It  is  best  to  cut  serial  sections,  and  time  can  be  saved  by  staining 
in  toto  with  borax-carmin  if  the  embryos  are  not  too  large  (not  more  than  10  mm.). 

While  much  can  be  learned  by  examining  a  series  of  sections,  it  is  advisable  to  recon- 
struct from  serial  sections  (see  Appendix)  the  developing  organs  in  one  or  two  stages. 
The  models  thus  obtained  are  extremely  useful  in  understanding  the  relations  of  the 
structures. 

After  the  embryo  has  attained  a  considerable  size,  very  careful  gross  dissections  will  often 
prove  instructive. 


386  TEXT-BOOK  OF  EMBRYOLOGY. 

References  for  Further  Study. 

BRACKET,  A.:  Recherches  sur  le  developpement  du  diaphragme  et  du  foie.  Jour,  de 
VAnat.  et  de  la  Physiol,  T.  XXXII,  1895. 

BROMAN,  J.:  Die  Entwickelungsgeschichte  der  Bursa  omentalis  und  ahnlicher  Recess- 
bildungen  bei  den  Wirbeltieren.  Wiesbaden,  1904. 

BROMAN,  I. :  Ueber  die  Entwickelung  und  Bedeutung  der  Mesenterien  und  der  Korper- 
hohlen  bei  den  Wirbeltieren.  Ergebnisse  der  Anal.  u.  Entwick.,  Bd.  XV,  1906. 

BROSSIKE,  G.:  Ueber  intraabdominale  (retroperitoneale)  Hernien  und  Bauchfelltaschen, 
nebst  einer  Darstellung  der  Entwickelung  peritonealer  Formationen.  Berlin,  1891. 

HERTWIG,  O. :  Lehrbuch  der  Entwickelungsgeschichte  des  Menschen  und  der  Wirbeltiere. 
Jena,  1906. 

KEIBEL,  F.,  and  MALL,  F.  P.:  Manual  of  Human  Embryology,  Vol.  I,  1910. 

KLAATSCH:  Zur  Morphologic  der  Mesenterialbildungen  am  Darmkanal  der  Wirbeltiere. 
Morph.  Jahrbuch,  Bd.  XVIII,  1892. 

KOLLMANN,  J.:  Lehrbuch  der  Entwickelungsgeschichte  des  Menschen.     Jena,  1898. 

KOLLMANN,  J.:   Handatlas  der  Entwickelungsgeschichte  des  Menschen.     Bd.  II,  1907. 

MALL,  F.  P.:  Development  of  the  Human  Coelom.     Jour,  of  Morphol.,  Vol.  XII,  1897. 

PIERSOL,  G.  A.:  Teratology.  In  Wood's  Reference  Handbook  of  the  Medical  Sciences. 
1904. 

RAVN,  E.:  Ueber  die  Bildung  der  Scheidewand  zwischen  Brust-  und  Bauchhohle  in 
Saugetierembryonen.  Arch.  f.  Anat.  u.  Physiol.,  Anat.  Abth.,  1889. 

STRAHL  and  CARIUS:  Beitrage  zur  Entwickelungsgeschichte  des  Herzens  und  der 
Korperhohlen.  Arch.  /.  Anat.  u.  Physiol.,  Anat.  Abth.,  1889. 

SWAEN,  A.:  Recherches  sur  le  developpement  du  foie,  du  tube  digestif,  de  1'arriere- 
cavite  du  peritoine  et  du  mesentere.  Premiere  partie,  Lapin.  Jour,  de  V Anat.  et  de  la 
Physiol.,  T.  XXXIII,  1896.  Seconde  partie.  Embryons  humains.  T.  XXXIII,  1897. 

TOLDT,  C.:  Bau  und  Wachstumsveranderung  der  Gekrose  des  menschlichen  Darm- 
kanals.  Denkschr.  der  kais.  Akad.  Wissensch.  Wien.  Math.-Naturwissen.  Classe,  Bd. 
XLI,  1879. 


CHAPTER  XV. 
THE  DEVELOPMENT  OF  THE  UROGENITAL  SYSTEM. 

No  other  system  in  the  body  presents  such  peculiarities  of  development  as 
ic  urogenital  system.  In  the  first  place,  it  is  exceedingly  complicated  on  ac- 
:ount  of  its  many  parts.  It  is  derived  from  both  mesoderm  (mesothelium  and 
mesenchyme)  and  entoderm.  The  urinary  portion  develops  into  a  great  com- 
plex of  ducts  for  the  carrying  off  of  waste  products.  The  genital  portion  in 
both  sexes  becomes  highly  specialized  for  the  production  and  carrying  off 
of  the  sexual  elements.  In  the  second  place,  instead  of  one  set  of  urinary  organs 
developing  and  persisting,  three  sets  develop  at  different  stages.  The  first 
set  (the  pronephroi)  disappears  in  part,  but  leaves  certain  structures  which  are 
used,  so  to  speak,  in  the  development  of  the  second.  The  second  set  (themeso- 
nephroi)  disappears  for  the  most  part,  leaving,  however,  some  portions  which 
are  taken  up  in  the  development  of  the  genital  organs  and  other  portions  which 
persist  as  rudimentary  structures  in  the  adult.  The  third  set  (the  metanephroi 
or  kidneys)  develops  in  part  from  the  second  and  in  part  is  of  independent 
origin.  These  conditions  afford  one  of  the  most  striking  examples  of  the  repe- 
tition of  the  phylogenetic  history  by  the  ontogenetic,  or,  in  other  words,  of  von 
Baer's  law  that  an  individual,  in  its  development,  has  a  tendency  to  repeat  its 
ancestral  history;  for  the  first  and  second  sets  of  urinary  organs  in  the  human 
embryo  represent  systems  that  are  permanent  in  the  lower  Vertebrates.  In  the 
third  place,  the  ducts  of  the  genital  organs  are  not  homologous  in  the  two  sexes. 
In  the  male  the  ducts  (deferent  duct,  duct  of  the  epididymis,  efferent  ductules) 
are  derived  from  the  second  set  of  urinary  organs;  in  the  female  they  (the 
oviducts)  are  derived  from  other  ducts  which  develop  in  the  second  set  of 
urinary  organs,  but  which  are  not  functionally  a  part  of  the  latter. 

THE  PRONEPHROS. 

The  pronephros,  with  the  pronephric  duct,  is  the  first  of  the  urinary  organs 
to  appear.  In  embryos  of  2-3  mm.  there  are  two  pronephric  tubules  on  each 
side,  situated  at  the  level  of  the  heart.  Although  their  mode  of  origin  has  not 
been  observed  in  the  human  embryo,  it  is  probable,  judging  from  observations 
on  lower  Vertebrates,  that  they  arise  as  evaginations  of  the  mesothelium.  The 
part  of  the  mesothelium  involved  is  that  adjacent  to  the  intermediate  cell  mass 
(Fig.  343) .  (The  intermediate  cell  mass  is  the  portion  of  the  mesoderm  interven- 
ing between  the  primitive  segments  and  the  unsegmented  parietal  and  visceral 

387 


388 


TEXT-BOOK  OF  EMBRYOLOGY. 


layers;  p.  84.)  The  more  cephalic  of  the  two  tubules  becomes  hollow  and 
opens  into  the  ccelom;  the  more  caudal  is  merely  a  solid  cord  of  cells.  Neither 
tubule  forms  any  connection  with  the  pronephric  duct.  At  each  side  of  the  root 
of  the  mesentery  a  small  elevation,  which  projects  into  the  ccelom,  probably 
represents  a  rudimentary  glomerulus.  A  glomerulus  in  the  lower  Vertebrates, 
where  the  pronephros  develops  to  a  much  greater  degree  than  in  Mammals, 
contains  tortuous  vessels  derived  from  branches  of  the  aorta  (Fig.  344). 
The  mesonephros  (p.  389),  beginning  to  develop  almost  as  soon  as  the  pro- 
nephros and  in  the  same  relative  position,  forms  a  ridge  which  projects  into  the 
ccelom.  The  pronephric  tubules  thus  become  embedded  in  the  mesonephric 
ridge. 

The  pronephric  duct  begins  to  develop  about  the  same  time  as  the  tubules. 
It  appears  as  a  longitudinal  ridge  on  the  outer  side  of  the  intermediate  cell  mass 

Sclerotomo       Mvotome 


Entodernr 


FIG.  343. — Transverse  section  of  a  dog  embryo  with  19  primitive  segments.     Bonnet. 
Section  taken  through  sixth  segment. 


at  the  level  of  the  heart  and  projects  into  the  space  between  the  mesoderm  and 
ectoderm.  The  ridge  is  at  first  solid  but  soon  acquires  a  lumen,  and  gradually 
extends  to  the  caudal  end  of  the  embryo  where  it  bends  medially  to  open  into 
the  gut.  The  origin  of  the  caudal  portion  of  the  duct  is  a  matter  of  dispute. 
It  comes  in  contact  and  fuses  with  the  ectoderm,  but  whether  in  the  higher  ani- 
mals the  fusion  is  secondary  or  signifies  a  derivation  from  the  ectoderm  has 
not  been  determined.  When  first  formed,  the  entire  duct  lies  on  the  outer  side 
of  the  intermediate  cell  mass,  but  later  becomes  embedded  in  the  mesonephric 
ridge  (p.  391). 

The  pronephric  tubules  are  but  transient  structures  and  have  no  functional 
significance  in  man  and  the  higher  Vertebrates.  The  ducts,  however,  remain 
and  become  the  ducts  of  the  second  set  of  urinary  organs,  the  mesonephroi. 

The  significance  of  the  pronephros  can  be  understood  only  by  reference  to  the  conditions 
in  the  lower  animals.  In  the  latter  the  pronephros  acquires  a  relatively  higher  degree  of  de- 


THE   DEVELOPMENT   OF  THE  UROGENITAL  SYSTEM.  389 

velopment  than  in  the  higher  forms.  The  tubules  are  segmentally  arranged  and  are  present 
in  many  segments  of  the  body.  They  open  at  their  outer  ends  into  the  ducts,  and  at  their 
inner  ends  into  the  ccelom  through  ciliated  funnel-shaped  mouths  or  nephrostomes.  Little 
masses  of  mesoderm,  containing  tortuous  vessels  derived  from  branches  of  the  aorta,  form 
glomeruli  which  project  into  the  ccelom.  Waste  products  are  removed  from  the  blood 
through  the  agency  of  the  glomeruli  and  are  collected  in  the  ccelom.  They  are  then  taken  up 
by  the  pronephric  tubules  and  carried  away  by  the  ducts.  In  some  of  the  Round  Worms 
there  is  not  even  a  longitudinal  duct,  but  the  tubules  open  directly  on  the  outer  surface  of 
the  body.  In  the  lowest  Fishes  all  the  tubules  on  each  side  open  into  a  longitudinal  duct 
which  opens  into  the  cloaca.  In  these  lower  forms  of  animal  life  the  pronephroi  constitute 
the  permanent  urinary  apparatus.  In  the  ascending  scale  the  mesonephroi  appear  (higher 


Nch. 

X-N      L^J      r^\    1 

Pron.  t. 


Glom. 


FIG.  344. — Diagram  of  the  pronephric  system  in  an  amphibian.     Bonnet. 

Ccel.,  Ccelom;  Glom.,  glomerulus,  containing  ramifications  of  a  branch  of  the  aorta; 

Nch.,  notochord;  Pron.  t.,  pronephric  tubule. 

Fishes,  Amphibia)  and  assume  the  function  of  carrying  off  waste  products.  The  prone- 
phroi also  develop,  but  to  a  lesser  degree.  Still  higher  in  the  scale  (Reptiles,  Birds,  Mam- 
mals) the  kidneys  (metanephroi)  appear  and  the  mesonephroi  lose  their  functional  sig- 
nificance. But  even  in  the  very  highest  Mammals  the  pronephroi  appear,  in  a  very  rudimen- 
tary form,  in  each  individual  in  the  earliest  embryonic  stages,  thus  repeating  the  ancestral 
history. 

THE  MESONEPHROS. 

The  mesonephroi,  which  constitute  the  second  set  of  urinary  organs,  appear 
in  embryos  of  2.6-3.0  mm.,  immediately  following  the  pronephroi.  They  be- 
gin to  develop  just  caudal  to  the  pronephric  tubules  and  in  the  same  relative 
position  as  the  latter,  that  is,  in  the  intermediate  cell  mass.  Condensations* 
appear  in  the  mesenchyme  and  become  more  or  less  tortuous.  At  their  inner 
ends  they  form  secondary  connections  with  the  mesothelium  and  at  their  outer 
ends  they  join  the  pronephric  duct  which  now  becomes  the  mesonephric  (or 
Wolffian)  duct.  The  cells  acquire  an  epithelial  character,  lumina  appear, 
and  the  tortuous  mesenchymal  condensations  thus  become  true  tubules.  Their 
connections  with  the  mesothelium  soon  disappear  (Fig.  345). 

*The  term  "condensation"  is  here  used  to  mean  increased  density  of  tissue  due  mainly  to 
proliferation  of  cells. 


390 


TEXT-BOOK  OF  EMBRYOLOGY. 


After  the  tubules  are  formed,  other  condensations  of  the  mesenchyme  appear 
near  their  inner  ends.  A  branch  from  the  aorta  enters  each  condensation  and 
breaks  up  into  a  number  of  smaller  vessels  which  ramify  inside,  the  entire 
structure  thus  becoming  a  glomerulus.  Each  glomerulus  pushes  against  the 
corresponding  tubule,  the  latter  becoming  flattened  and  then  growing  around 
the  glomerulus.  In  this  way  the  glomerulus  becomes  surrounded  by  two  layers 
of  epithelium,  except  at  the  point  where  the  vessels  enter,  and  the  whole  structure 
— the  Malpighian  corpuscle — resembles  very  closely  a  renal  corpuscle  of  the  adult 


Roof         Spinal 
plate      ganglion 


Amnion 


Glomerulus 


Mesentery 


Intestine 


Post,  cardinal  vein 


Mesonephric 
(Wolffian)  duct 


Blood  vessel 

Mesonephric 
(Woiffian)  ridge 


Coslom 

Body  wall  with 
umbilical  vein 


FIG.  345.  —  From  a  transverse  section  of  a  sheep  embryo  of  21  days  (15  mm.), 
showing  the  developing  mesonephros.     Bonnet. 


kidney.  Waste  products  are  removed  from  the  blood  through  the  agency  of 
the  glomeruli  and  are  carried  to  the  ducts  by  the  mesonephric  tubules  (Fig.  345). 
The  tubules  themselves  increase  in  length  and  become  much  coiled.  Sec- 
ondary and  tertiary  tubules  also  develop  and  become  branches  of  the  primary, 
Whether  these  develop  from  condensations  of  the  mesenchyme  or  as  buds  from 
the  primary  tubules  has  not  been  determined.  Each  tubule  consists  of  two 
parts  —  (i)  a  dilated  part  around  the  glomerulus,  composed  of  large  flat  cells 
and  forming  Bowman's  capsule,  and  (2)  a  narrower  coiled  part  leading  from 


THE   DEVELOPMENT   OF  THE  UROGENITAL  SYSTEM.  391 

the  glomerulus  to  the  duct  and  composed  of  smaller  cuboidal  cells  (Fig.  345). 
The  primary  mesonephric  tubules  are  arranged  segmentally,  one  appearing 
in  each  segment  as  far  back  as  the  pelvic  region.  Thus  the  intermediate  cell 
mass  may  be  considered  as  a  series  of  nephrotomes,  corresponding  to  the 
sclerotomes  and  myotomes.  The  segmental  character  is  soon  lost,  however, 
owing  to  the  inequality  of  growth  between  the  mesonephros  and  the  other  seg- 
mental structures,  and  to  the  development  of  the  secondary  and  tertiary  tubules. 
As  stated  above,  the  first  mesonephric  tubules  appear  immediately  caudal  to 


Mid-brain 


^_.   ,.     „  __  •  Fore-brain 

Hind-brain 

Branchial  groove  I 


Heart— Jf- 


Intestine 


Mesonephros — 

^^^^^^H  :£! Genital  ridge 

Ccelom «I1 

'*  J£f/- Body  wall 

Lower  limb  bud fPB  0 Genital  eminence 


Tail 


FIG.  346. — Human  embryo  of  5  weeks.     The  ventral  body  wall  has  been  removed 
to  disclose  the  mesonephroi.     Kollmann. 

the  pronephros.  From  this  point  their  formation  gradually  progresses  in  a 
caudal  direction  as  far  as  the  pelvic  region.  By  the  further  development  of  the 
primary  and  by  the  addition  of  the  secondary  and  tertiary  tubules  and  the 
glomeruli,  the  mesonephros  as  a  whole  increases  in  size  and  forms  a  large 
structure  which  projects  into  the  ccelom  on  each  side  of  the  body,  forming  the 
so-called  mesonephric  or  Wolffian  ridge.  It  reaches  the  height  of  its  develop- 
ment in  the  human  embryo  about  the  fifth  or  sixth  week,  at  which  time  it  ex- 
tends from  the  region  of  the  heart  to  the  pelvic  region  (Fig.  346).  Each  organ 


392 


TEXT-BOOK  OF  EMBRYOLOGY. 


is  attached  to  the  dorsal  body  wall  by  a  distinct  mesentery  which,  at  its  cephalic 
end,  also  sends  off  a  band  to  the  diaphragm — the  diaphragmatic  ligament  of 
the  mesonephros.  The  peritoneum  is  reflected  over  the  surface  of  the  meso- 
nephros,  and  on  the  ventro-medial  side  the  mesothelium  becomes  thickened  to 
form  the  genital  ridge  (p.  407 ;  Figs.  3 14  and  346) .  The  mesonephric  ducts  are 
embedded  in  the  lateral  parts  of  the  organs  and  extend  throughout  practically 
their  entire  length.  Since  the  ducts  are  identical  with  the  pronephric  ducts, 
they  open  at  first  into  the  caudal  end  of  the  gut,  or  cloaca  (p.  388;  Fig.  360). 
At  a  little  later  period,  when  the  urogenital  sinus  is  formed,  they  open  at  the 
junction  of  the  latter  with  the  bladder  (Fig.  363) .  Still  later  they  open  into  the 


Appendage 


Testicle 


Appendage  of  epididymis 


Mesonephric  duct 
(duct  of  epididymis) 


*!  —  -Paradidymis 


..  Aberrant  ductule 


Mullerian  duct 


-     Urogenital  sinus 


FIG.  347. — Diagram  representing  certain  persistent  portions  of  the  mesonephros 
in  the  male  (see  table).     Kollmann. 

sinus  itself  (p.  403).  A  description  of  their  further  development  is  best  deferred 
to  the  section  on  the  male  genital  organs,  since  they  become  the  genital  ducts 
(p.  420). 

The  mesonephroi  function  as  urinary  organs  during  the  period  of  their 
existence  in  the  embryos  of  all  higher  Vertebrates.  Excretory  products  are  con- 
veyed directly  to  the  tubules  by  means  of  the  glomeruli  instead  of  being  de- 
posited in  the  ccelom  and  then  taken  up  by  the  tubules,  as  is  the  case  in  func- 
tional pronephroi  (p.  389).  The  main  excretory  ducts  are  the  same  as  in  the 
pronephroi.  Aside  from  the  vessels  in  the  glomeruli  the  mesonephroi  are  ex- 
ceedingly vascular  organs.  Large  and  small  branches  of  the  posterior  cardinal 
veins  ramify  among  the  tubules  (Figs.  314  and  232).  The  blood  undergoes 


THE   DEVELOPMENT   OF  THE   UROGENITAL  SYSTEM. 


393 


purifying  processes  in  its  close  contact  with  the  tubules  and  is  returned  to  the 
heart  by  the  posterior  cardinals,  or,  after  the  cephalic  ends  of  the  latter  atrophy, 
by  the  subcardinals  and  the  inferior  vena  cava  (see  p.  258;  also  Fig.  232,  B). 
There  is  thus  present  a  true  renal  portal  system,  similar  to  the  hepatic  portal 
system. 

Although  the  mesonephroi  become  large  functional  organs  during  the  earlier 
stages  of  development,  they  atrophy  and  disappear  for  the  most  part,  coinci- 
dently  with  the  appearance  and  development  of  the  kidneys.  The  degeneration 
begins  during  the  sixth  or  seventh  week  and  goes  on  rapidly  until,  by  the  end  of 
the  fourth  month,  little  remains  but  the  ducts  and  a  few  tubules.  The  degenera- 


o.  t.  a. 


Ovd. 


Epo.  1. 


Epo.  t. 


FIG.  348. — Diagram  representing  certain  persistent  portions  of  the  mesonephros 

in  the  female  (see  table). 
Epo.  1.,  Longitudinal  duct  of  the  epoophoron;  Epo.  t.,  transverse  ductules  of  the  epoophoron;  O.  t,  a., 
ostium  abdominale  tubae;  Ovd.,  oviduct;  X  represents  a  small  duct  which,  if  present,  leads 
from  the  epoophoron  to  one  of  the  fimbriffi  of  the  oviduct. 

tive  processes  consist  of  (i)  an  ingrowth  of  connective  tissue  among  the  tubules, 
(2)  atrophy  of  the  epithelium  of  the  tubules,  and  (3)  atrophy  of  the  glomeruli. 
The  portions  which  remain  differ  in  the  two  sexes,  and  since  the  remnants 
are  taken  up  in  the  formation  of  the  male  and  female  genital  organs  it  seems 
best  to  discuss  them  more  fully  under  those  heads  (pp.  417, 420).  The  accom- 
panying table,  however,  will  give  a  clue  to  their  fate  (see  also  Figs.  347  and 
348).  A  more  comprehensive  table  will  be  found  on  p.  427. 

Male  Female 


Mesonephros 


Cephalic  part 
Caudal  part 


Duct  of  mesonephros 


Efferent      ductules 
(vasa  efferentia) 

f  Paradidymis 
1  Vasa  aberrantia 
Deferent  duct 
Ejaculatory  duct 
Seminal  vesicles 


Epoophoron 
J 
I  Paroophoron 

I  Gartner's  canals 


The  significance  of  the  mesonephroi,  which,  as  well  as  the  pronephroi,  are  present  in  the 
embryos  of  ail  higher  Vertebrates,  can  be  understood  only  by  referring  to  the  conditions  in  the 
lower  Vertebrates.  In  the  majority  of  the  Fishes  and  in  the  Amphibia  the  mesonephroi  con- 
stitute the  functional  urinary  organs  of  the  adult  and  possess  essentially  the  same  structure  as 


394  TEXT-BOOK  OF  EMBRYOLOGY. 

in  the  embryos  of  higher  forms.  Beginning  in  the  Reptiles  and  continuing  up  through  the 
series  of  Birds  and  Mammals,  another  set  of  urinary  organs — the  kidneys — develops.  The 
mesonephroi  also  develop  in  these  forms,  even  to  a  high  degree,  thus  repeating  the  ancestral 
history,  but  retain  their  original  function  only  in  the  earlier  embryonic  stages. 

THE  KIDNEY  (METANEPHROS). 

The  kidneys  are  the  third  set  of  urinary  organs  to  develop.  They  assume 
the  function  of  the  mesonephroi  as  the  latter  atrophy,  and  constitute  the  per- 
manent urinary  apparatus.  Each  kidney  is  derived  from  two  separate  anlagen 
which  unite  secondarily.  The  epithelium  of  the  ureter,  renal  pelvis,  and 
straight  renal  tubules  (collecting  tubules)  is  derived  from  the  mesonephric  duct 


Mesonephros 


Mesonephric  duct 

•  Metanephric  blastema 


Metanephric  blastema 
(inner  zone) 

~—  Primitive  renal  pelvis 

' '    -  -  '  _:-  :  ^ ' 


Urete 


FIG.  349. — From  a  reconstruction  of  the  anlage  of  the  kidney  (metanephros).  etc.,  of  a  human 
embryo  at  the  beginning  of  the  5th  week.     Schreiner. 

by  a  process  of  evagination.  The  convoluted  renal  tubules  and  glomeruli  are 
derived  directly  from  the  mesenchyme,  and  in  this  respect  resemble  the  meso- 
nephric tubules  and  glomeruli. 

The  Ureter,  Renal  Pelvis  and  Straight  Renal  Tubules. — During  the 
fourth  week  (in  embryos  of  about  5  mm.)  a  small,  hollow,  bud-like  evagination 
appears  on  the  dorsal  side  of  each  mesonephric  duct  near  its  opening  into  the 
cloaca.  The  evagination  continues  to  grow  dorsally  in  the  mesenchyme 
toward  the  vertebral  column,  and  at  the  same  time  becomes  differentiated 
into  two  parts,  a  narrow  stalk  and  a  dilated  terminal  portion.  The  stalk  is 
the  forerunner  of  the  ureter,  the  dilated  end  is  the  primitive  renal  pelvis  (Figs. 
349  and  351).  When  the  dilated  end  reaches  the  ventral  side  of  the  vertebral 


THE  DEVELOPMENT   OF  THE   UROGENITAL  SYSTEM. 


395 


column  it  turns  and  grows  cranially  between  the  latter  and  the  mesonephros. 
The  stalk  (or  ureter)  elongates  accordingly  (Fig.  350). 

About  the  fifth  week,  four  evaginations  from  the  primitive  renal  pelvis  appear 
—one  cephalic,  one  caudal  and  two  central  (Figs.  350  and  352).  These  may  be 
considered  as  straight  renal  tubules  of  the  first  order.  The  distal  end  of  each 
then  enlarges  to  form  a  sort  of  ampulla,  and  from  each  ampulla  two  other 
evaginations  develop,  forming  tubules  of  the  second  order.  From  the  ampulla 
of  each  secondary  tubule  two  tertiary  tubules  grow  out;  and  this  process  con- 


Mesonephros 


Mesonephric  dui 


Junction  of  meson, 
duct  and  ureter 


Cephalic  evagination 


_) Metanephric  blasterr.a 


Central  evaginations 


-, —  Caudal  evagination 


FIG.  350. — From  a  reconstruction  of  the  anlage  of  the  kidney,  etc.,  of  a  human 
embryo  of  11.5  mm.     Schreincr. 

tinues  in  a  similar  manner  until  twelve  or  thirteen  divisions  occur,  the  final 
divisions  occurring  during  the  fifth  month.  The  tubules  grow  into  the  mesen- 
chyme  which  surrounds  the  pelvis  and  which  forms  the  so-called  metanephric 
blastema,  or  nephro genie  tissue  (Fig.  351). 

If  the  straight  tubules  were  to  remain  in  this  condition,  only  four  would  open 
directly  into  the  pelvis,  corresponding  with  the  four  primary  evaginations.  In 
the  adult,  however,  many  hundreds  open  into  the  pelvis;  consequently  extensive 
changes  of  the  early  condition  must  take  place.  These  changes  are  similar  to 


396 


TEXT-BOOK  OF  EMBRYOLOGY. 


the  process  by  which  the  proximal  ends  of  some  of  the  blood  vessels  come  to  be 
included  in  the  wall  of  the  heart  (p.  231).  The  proximal  ends  of  the  tubules 
become  wider,  the  pelvis  swells  out,  and  the  walls  of  the  tubules  become  in- 
cluded in  the  wall  of  the  pelvis.  In  certain  parts  of  the  pelvic  wall  this  process 
goes  on  until  deep  bays — the  calyces — are  formed,  into  which  a  large  number  of 
tubules  open.  In  the  other  parts  of  the  wall  the  process  does  not  go  so  far,  thus 
leaving  promontories — the  renal  papilla — upon  which  larger  tubules  or  papil- 
lary ducts  open.  The  adult  renal  pelvis  thus  consists  of  the  primitive  pelvis  plus 
the  proximal  ends  of  the  straight  tubules. 


Metanephric 
blastema 


Primitive 
renal  pelvis 


Ureter 

Mesonephric  duct 
Intestine 

Bladder 


FIG.  351. — From  a  transverse  section  of  a  human  embryo  at  the  beginning  of  the  5th  week. 
The  plane  of  the  section  is  indicated  in  Fig.  349.     Schreiner. 


The  Convoluted  Renal  Tubules  and  Glomeruli.— As  stated  above, 
the  metanephric  blastema  or  nephrogenic  tissue  surrounds  the  renal  pelvis 
and  the  straight  tubules.  It  represents  a  condensation  of  the  mesenchyme  and  is 
destined  to  give  rise  to  the  convoluted  tubules  and  glomeruli.  The  cells  of  the 
blastema  in  the  region  of  the  ampullae  of  the  terminal  straight  tubules  acquire 
an  epithelial  character  and  become  arranged  in  solid  masses  (Fig.  353).  Each 
mass  unites  with  an  ampulla  and  acquires  a  lumen,  which  becomes  continuous 
with  the  lumen  of  the  straight  tubule,  then  elongates  and  forms  an  S-shaped 
structure  (Figs.  354  and  355).  The  loop  of  the  S  nearer  the  straight  tubules 
elongates  still  more  and  grows  toward  the  pelvis,  parallel  with  the  straight 


THE   DEVELOPMENT   OF  THE   UROGENITAL  SYSTEM.  397 

tubules,  to  form  Henle's  loop.  The  part  between  Henle's  loop  and  the  straight 
tubule  elongates  and  becomes  convoluted  to  form  the  proximal  part  of  a  con- 
voluted renal  tubule  (second  convoluted  tubule).  The  part  between  the  distal 
end  and  Henle's  loop  elongates  and  becomes  convoluted  to  form  the  distal  part 
of  a  convoluted  renal  tubule  (first  convoluted  tubule)  (Figs.  356  and  357). 

To  avoid  confusion  it  may  be  well  to  call  attention  to  the  fact  that  what  has  here  been 
called  the  proximal  part  of  a  convoluted  tubule  corresponds  with  what  is  usually  described  as 
the  second  or  distal  convoluted  tubule,  and  that  the  distal  part  of  a  convoluted  tubule 
corresponds  with  the  first  or  proximal  convoluted  tubule.  In  histology  the  distal  and  proxi- 
mal convoluted  tubules  are  spoken  of  in  relation  to  the  renal  corpuscle,  but  in  development 
it  is  more  convenient  to  speak  of  the  terminal  part  of  a  tubule  as  its  distal  part. 


Caudal 
evagi  nation 


Ureter 


FIG.  352. — From  a  model  of  the  primitive  renal  pelvis  and  the  evaginations  which  form  the  cephalic, 
central  and  caudal  straight  renal  tubules  of  the  first  order.  Human  embryo  of  4^  months. 
Compare  with  Fig.  350.  Schreiner 

A  glomerulus  develops  in  connection  with  the  extreme  distal  end  of  a  con- 
voluted tubule  or,  in  other  words,  with  the  distal  loop  of  the  S  (p.  396).  There 
occurs  here  a  further  condensation  of  the  mesenchyme,  into  which  grows  a 
branch  from  the  renal  artery.  This,  as  the  afferent  vessel  of  the  glomerulus, 
breaks  up  into  several  arterioles,  each  of  which  gives  rise  to  a  tuft  of  capillaries. 
These  tufts  are  separated  from  one  another  by  somewhat  more  mesenchymal 
tissue  than  separates  the  capillaries  within  a  tuft.  The  tufts  with  the  asso- 
ciated mesenchymal  tissue  constitute  a  glomerulus,  and  it  is  the  mesenchymal 
septa  between  the  tufts  that  give  to  the  glomerulus  its  characteristic  tabulated 
appearance.  The  capillaries  of  each  tuft  empty  into  an  arteriole,  and  the 
several  arterioles  unite  to  form  the  efferent  vessel  of  the  glomerulus,  which  passes 
out  along  side  of  the  afferent  vessel.  The  renal  tubule  becomes  flattened  on  the 
side  next  the  condensation  of  the  mesenchyme,  and  as  the  glomerulus  develops, 
the  epithelium  of  the  tubule  grows  around  it  except  at  the  point  where  the  blood 


TEXT-BOOK  OF  EMBRYOLOGY. 


vessels  enter  and  leave.  Thus  a  double  layer  of  epithelium  comes  to  surround 
the  glomerulus,  the  space  between  the  two  layers  being  the  extreme  distal  part 
of  the  lumen  of  a  renal  tubule.  The  inner  layer  is  closely  applied  to  the  surface 


Anlagen  of 
convoluted 
renal  tubules 


Renal  pelvis 


Capsule 


Anlage  of 

convoluted  renal  tubule 

Ampulla  of 
straight  renal  tubule 


FIG.  353. — Sagittal  section  of  the  anlage  of  the  left  kidney  in  a  rabbit  embryo  of  15  days.   Schreiner. 
The  straight  renal  tubules  (sections  of  which  are  shown)  are  embedded  in  the  metanephric  blastema. 

Condensations  of  the  latter  form  the  anlagen  of  the  convoluted  renal  tubules.     At  the  left 

of  the  figure  several  mesonephric  tubules  are  shown. 


Amp. 


Con.  r.  t. 


Met.  bl. 


Con.  r.  t. 


FIG.  354. — From  a  section  of  the  kidney  of  a  human  foetus  of  7  montns.     Schreiner. 

Amp.,  Ampulla  of  a  straight  renal  tubule;  Con.  r.  t.,  anlagen  of  convoluted  renal  tubules,  above  and 

between  which  are  two  ampullae  (compare  Fig.  355);  met.  bl.,  metanephric  blastema. 

of  the  glomerulus  and  even  dips  down  into  the  latter  between  the  tufts.  The 
outer  layer  forms  Bowman's  capsule,  the  flat  epithelium  of  which  passes  over 
into  the  cuboidal  epithelium  of  the  "neck"  of  the  tubule,  and  this  in  turn  is 


THE   DEVELOPMENT   OF  THE   UROGENITAL  SYSTEM. 


399 


Prox.  convoluted  tubule 
Dist.  convoluted  tubule. 
Henle's  loo 


FIG.  355. 


Ampulla  of  straight  tubule 


Henle's  loop 

Distal  part  of 
convoluted  tubule 


Bowman's  capsule 


Proximal  part  of 
convoluted  tubule 


Distal  part  of 
convoluted  tubule 


"  Neck" 
Bowman's  capsule 


FIG.  356. 


Prox.  convoluted  tubule 
Dist.  convoluted  tubule 
Henle's  loop 


Prox.  convoluted  tubu 
Bowman's  capsule 
Straight  tubule 


Prox.  convoluted  tubule 
Dist.  convoluted  tubule 

Prox.  convoluted  tubule 


Dist.  convoluted  tubule 
—    Bowman's  capsule 

Ascending     "1 


Descending 


arm  of  Henle's  loop 


FIG.  357. 

FIGS.  355,  356  and  357. — From  reconstructions  of  convoluted  renal  tubules  in  successive 

stages  of  development.     Stoerk. 
26 


400 


TEXT-BOOK  OF  EMBRYOLOGY. 


continuous  with  the  pyramidal  epithelium  of  the  distal  convoluted  tubule. 
The  entire  structure  is  a  renal  corpuscle.  The  formation  of  renal  corpuscles 
begins  in  embryos  of  30  mm.  and  continues  until  after  birth. 

The  Renal  Pyramids  and  Renal  Columns. — The  tubules  arising  from 
the  four  primary  evaginations  of  the  renal  pelvis  together  form  four  distinct 
groups  or  primary  renal  (Malpighian)  pyramids — one  cephalic,  one  caudal,  and 
two  central.  The  central  pyramids  are  crowded  in  between  the  end  pyramids, 
(cephalic  and  caudal)  and  do  not  develop  as  rapidly  as  the  latter  which  soon 
bend  around  toward  the  ureter,  thus  resulting  in  the  formation  of  the  convex 
side  of  the  kidney  and  a  depression  or  hilus  opposite  (compare  Figs.  352  and 
358).  Between  these  four  pyramids  the  mesenchyme  remains  for  some  time  as 

Primary  renal  pyramid 


Cephalic  straight  tubule 


Central  straight  tubule -•— 


Caudal  straight  tubule 


Primary  renal  column 


Primary  renal  pyramid 


Primary  renal  column 


Ureter 

Primary  renal  pyramid 
FIG.  358. — Frontal  section  of  the  kidney  of  a  human  foetus  of  3!  months  (10  cm.).     Hauch. 

rather  distinct  septa,  forming  the  primary  renal  columns  (columns  of  Bertini) 
which  are  marked  by  corresponding  depressions  on  the  surface  of  the  kidney 
and  extend  to  the  renal  pelvis.  The  four  primary  pyramids  may  be  considered 
as  lobes  (Fig.  358).  It  should  also  be  stated  that  the  parts  of  the  tubules 
derived  from  the  mesenchyme  form  the  bases  of  the  renal  pyramids.  Be- 
tween the  groups  of  straight  tubules  derived  from  evaginations  of  the  second  or 
third  order  (see  p.  395)  there  are  also  septa  of  mesenchyme  which  divide  each 
primary  pyramid  into  two  or  three  secondary  pyramids.  These  septa  may 
be  considered  as  secondary  renal  columns  (Fig.  359).  Thus  the  entire  kidney 
is  divided  into  from  eight  to  twelve  secondary  pyramids.  Tertiary  renal 
columns  then  divide  incompletely  the  secondary  pyramids  into  tertiary  pyra- 


THE   DEVELOPMENT   OF  THE   UROGENITAL  SYSTEM. 


401 


mids.     These  are  apparent  on  the  surface  of  the  kidney  and  constitute  the 
surface  lobulation,  but  are  not  clearly  denned  in  the  interior. 

The  formation  of  renal  papillae  (p.  396)  corresponds  to  the  formation  of 
pyramids  only  to  a  certain  point,  for  some  of  the  tertiary  pyramids  appear  only 
near  the  surface  and  consequently  do  not  have  corresponding  papillae.  This 
accounts  for  the  fact  that  frequently  the  number  of  pyramids  apparent  on  the 
surface  does  not  correspond  with  the  number  of  papillae.  The  surface  lobula- 
tion is  very  plainly  marked  in  kidneys  up  to  and  for  a  short  time  after  birth.  It 
then  disappears  and  the  surface  becomes  smooth.  At  the  same  time  the  con- 
nective (mesenchymal)  tissue  of  the  renal  columns  is  largely  replaced  by  the 

Secondary 

renal 
column    Secondary 

renal 

pyramid       Secondary 
renal 
column 


FIG.  359. — Frontal  section  of  the  kidney  of  a  human  foetus  of  19  weeks  (17.5  cm.).     Hauch. 

epithelial  elements  of  the  gland  so  that  in  the  adult  kidney  the  columns  are  not 
clearly  denned. 

The  capsule  of  the  kidney  is  derived  from  the  mesenchyme  which  surrounds 
the  anlage  of  the  organ  (Fig.  353) .  This  mesenchyme  is  transformed  into  fibrous 
connective  tissue  and  a  small  amount  of  smooth  muscle,  forming  a  layer  which 
closely  invests  the  kidney  and  dips  into  the  hilus  where  it  surrounds  the  blood 
vessels  and  the  end  of  the  ureter.  The  connective  tissue  and  muscle  of  the 
ureter  are  also  derived  from  the  mesenchyme. 

CORTEX  AND  MEDULLA. — As  the  convoluted  renal  tubules  develop  in  the 
metanephric  blastema  (p.  396) ,  they  form  a  cap-like  mass  around  the  group  of 


402  TEXT-BOOK  OF  EMBRYOLOGY. 

straight  tubules.  This  is  the  beginning  of  the  renal  cortex.  A  true  cortex, 
however,  can  be  spoken  of  only  after  the  appearance  of  the  glomeruli  (in 
embryos  of  30  mm.).  Its  peripheral  boundary  is  the  capsule,  and  the  renal 
corpuscles  nearest  the  pelvis  mark  its  inner  boundary.  The  mass  of  straight 
tubules  forms  the  bulk  of  the  medulla.  It  does  not  at  this  stage  contain  Henle's 
loops,  the  latter  developing  later  (during  the  fourth  month).  Both  cortex 
and  medulla  increase  until  the  kidney  reaches  its  adult  size.  The  cortex 
increases  relatively  faster  than  the  medulla  up  to  the  seventh  year;  after 
this  the  increase  is  practically  equal.  The  medullary  rays  are  probably 
secondary  formations,  being  formed  by  groups  of  straight  tubules  which 
grow  out  into  the  cortex;  later,  ascending  arms  of  Henle's  loops  are  added  to 
these  groups. 

Some  of  the  glomeruli  of  the  first  generation  are  much  larger  than  any 
found  in  the  adult.  In  some  of  the  lower  Mammals  these  "giant"  glomeruli 
disappear  and  it  is  probable  that  the  same  occurs  in  the  human  embryo.  Some 
of  the  tubules  also  degenerate  and  disappear.  The  cause  of  these  phenomena 
is  not  known. 

Changes  in  the  Position  of  the  Kidneys. — As  has  already  been  described 
(p.  394),  the  kidney  buds  first  grow  dorsally  from  the  mesonephric  ducts 
toward  the  vertebral  column.  They  then  grow  cranially,  with  a  corresponding 
elongation  of  the  ureters,  and  in  embryos  of  20  mm.  they  lie  for  the  most  part 
cranial  to  the  common  iliac  arteries.  This  migration  continues  until  the  time 
of  birth  when  the  cephalic  ends  of  both  kidneys  reach  the  eleventh  thoracic  ver- 
tebra. When  the  kidneys  begin  to  move  cranially  the  hilus  is  directed  caudally. 
Later  they  rotate  and  the  hilus  is  turned  toward  the  medial  sagittal  plane. 

Since  the  ureter,  renal  pelvis  and  straight  tubules  develop  from  the  mesonephric  ducts, 
and  since  the  convoluted  tubules  and  glomeruli  develop  directly  from  the  same  tissue  as  the 
mesonephric  tubules,  namely,  the  mesenchyme,  the  renal  tubules  may  be  said  to  represent 
the  third  generation  of  urinary  tubules.  But  no  definite  reason  for  the  appearance  of  the 
third  generation  can  be  given.  The  atrophy  of  the  mesonephroi  would,  of  course,  make 
necessary  the  compensatory  development  of  new  structures;  but  this  only  carries  the  problem 
a  step  further  back,  for  the  cause  of  the  atrophy  of  the  mesonephroi  is  not  clear.  In  regard 
to  this  atrophy,  however,  there  is  a  suggestion  of  a  cause  in  the  fact  that  in  the  Amphibia 
the  mesonephroi  are  in  part  used  for  conveying  the  sexual  elements,  which  leaves  the  meso- 
nephroi less  free  to  function  as  urinary  organs.  Possibly  the  loss  of  freedom  to  function  leads 
to  the  development  of  new  structures — the  kidneys — in  the  higher  forms  (Reptiles,  Birds 
and  Mammals).  In  these  forms  the  kidneys  assume  the  urinary  function  after  the  early 
embryonic  stages,  and  only  the  ducts  and  a  part  of  the  tubules  of  the  mesonephroi  persist  in 
the  male  to  convey  the  sexual  elements.  Thus  the  persistent  parts  of  the  mesonephroi  as- 
sume a  new  function  as  the  old  one  is  lost.  But,  on  the  other  hand,  complications  arise 
on  account  of  the  fact  that  in  the  female  the  sexual  products  are  carried  off  by  another  set 
of  ducts  (the  Miillerian  ducts),  which  develop  in  both  sexes  but  disappear  in  the  male, 
while  the  mesonephroi  and  their  ducts  disappear  almost  entirely. 


THE   DEVELOPMENT   OF  THE   UROGENITAL   SYSTEM. 


403 


THE  URINARY  BLADDER,  URETHRA  AND  UROGENITAL  SINUS. 

As  described  elsewhere,  the  allantois  appears  at  an  early  stage  as  an  evagi- 
nation  from  the  ventral  side  of  the  caudal  end  of  the  primitive  gut  (Fig.  282), 
grows  out  into  the  belly  stalk,  and  finally  becomes  enclosed  in  the  umbilical  cord 
(p.  118).  As  the  embryo  develops,  the  proximal  end  of  the  allantois  becomes 
elongated  to  form  a  stalk  or  duct  which  extends  from  the  caudal  end  of  the 
gut  to  the  umbilicus  (Fig.  285).  The  portion  of  the  gut  immediately  caudal  to 
the  attachment  of  the  allantoic  duct  becomes  dilated  to  form  the  cloaca  which 
at  first  is  a  blind  sac,  its  cavity  being  separated  from  the  outer  surface  of  the 
embryo  by  the  cloacal  membrane  (Fig.  360) .  The  latter  is  composed  of  a  layer  of 
entoderm  and  a  layer  of  ectoderm,  with  a  thin  layer  of  mesoderm  between.  The 
cloaca  then  becomes  separated  into  two  parts — a  larger  ventral  part  which  forms 


Mesoneohric  duct 


Intestine        Kidney  bud 
f\\ 


Cloacal  membrane 


Caudal  gut 

Notochord 

Neural  tube 


FIG.  360. — From  a  model  of  the  cloaca  and  the  surrounding  structures  in  a 
human  embryo  of  6.5  mm.     Keibel. 

, 

the  urogenital  sinus  and  a  smaller  dorsal  part  which  forms  the  rectum.  This 
is  accomplished  by  a  fold  or  ridge  which  grows  from  the  lateral  wall  into  the 
lumen  and  meets  and  fuses  with  its  fellow  of  the  opposite  side.  The  fusion  be- 
gins at  the  cephalic  end,  in  the  angle  between  the  allantoic  duct  and  the  gut, 
and  gradually  proceeds  caudally  until  the  separation  is  complete  as  far  as  the 
cloacal  membrane.  The  mass  of  tissue  forming  the  partition  is  called  the  uro- 
rectalfold  (Fig.  361).  The  openings  of  the  mesonephric  ducts,  which  primarily 
were  situated  in  the  lateral  cloacal  wall  (p.  392),  are  situated  after  the  separation 
in  the  dorso-lateral  wall  of  the  urogenital  sinus  (compare  Figs.  360,  361,  362). 
During  the  separation  of  the  urogenital  sinus  from  the  rectum,  certain 
changes  take  place  in  the  proximal  ends  of  the  mesonephric  ducts  and  ureters. 
The  ends  of  the  ducts  become  dilated  and  are  gradually  taken  up  into  the  wall  of 
the  sinus.  This  process  of  absorption  continues  until  the  ends  of  the  ureters  are 
included,  with  the  result  that  the  ducts  and  ureters  open  separately,  the  latter 


404  TEXT-BOOK  OF  EMBRYOLOGY. 

slightly  cranial  and  lateral  to  the  former.  (Compare  Figs.  362  and  363.)  This 
condition  is  reached  in  embryos  of  12  to  14  mm.  The  point  at  which  these  two 
sets  of  ducts  open  marks  the  boundary  between  a  slightly  larger  cephalic  part 
of  the  sinus,  the  anlage  of  the  bladder,  and  a  smaller  caudal  part  which  becomes 
the  urethra  and  urogenital  sinus  (Fig.  363). 

After  the  second  month  the  bladder  becomes  larger  and  more  sac-like,  and 
the  openings  of  the  ureters  migrate  farther  cranially  to  their  final  position.  The 
lumen  of  the  bladder  is  at  first  continuous  with  the  lumen  of  the  allantoic  duct, 
but  the  duct  degenerates  into  a  solid  cord  of  cells,  the  urachus.  The  latter 
degenerates  still  further  and  finally  remains  only  as  the  middle  umbilical  liga- 

Urorectal  fold  Mesonephric  duct 

Kidney  bud. 

Urachus 


Cloaca  <^ 

Urogenital  sinus  — 


,__  ,^___, .  — ,-_ — Rectum 
Cloacal  membrane 


:audal  gut 


FIG.  361. — From  a  model  of  the  cloacal  region  of  a  human  embryo  slightly  older  than 

that  shown  in  Fig.  360.     Keibel. 

The  arrow  points  to  the  developing  partition  (urorectal  fold)  between  the  rectum  and  urogenital 
sinus.  The  opening  of  the  mesonephric  duct  into  the  urogenital  sinus  is  indicated  by  a 
small  seeker. 

ment.  It  seems  quite  probable  that  the  bladder  is  derived  almost  wholly  from 
the  cloaca.  A  small  part  arises  from  the  inclusion  of  the  ends  of  the  mesoneph- 
ric ducts.  If  any  part  is  derived  from  the  allantoic  duct,  it  is  only  the  apex. 
After  the  bladder  begins  to  enlarge,  the  adjacent  portion  of  the  urogenital 
sinus  becomes  slightly  constricted.  This  marks  the  beginning  of  the  urethra. 
In  the  female  the  constricted  part  represents  practically  the  entire  urethra. 
In  the  male  it  represents  only  the  proximal  end,  the  other  portion  developing 
in  connection  with  the  penis  (p.  428).  The  urogenital  sinus  is  narrow  and 
tubular  at  its  junction  with  the  urethra;  more  distally  it  is  wider  and  is  shut  off 
from  the  exterior  by  the  cloacal  membrane.  After  the  embryo  reaches  a  length 
of  1 6  to  17  mm.,  the  membrane  ruptures  and  the  sinus  opens  on  the  surface. 


THE   DEVELOPMENT  OF  THE  UROGENITAL  SYSTEM. 


405 


The  narrow  part  of  the  sinus  is  gradually  taken  up  into  the  wider,  resulting  in 
the  formation  of  a  sort  of  vestibule.  In  both  sexes  the  urethra  opens  into  the 
deeper  end  of  the  vestibule.  In  the  male  the  mesonephric  (seminiferous) 


Cloaca 
(undivided  portion) 


Cloacal  membrane  ~ 


Tail 


Mesonephric  ducts 


_   Coelom 


—  Primitive  renal  pelvis 


Rectum 


FIG.  362. — From  a  reconstruction  of  the  caudal  end  of  a  human  embryo 
of  11.5  mm.  (4^  weeks).     Keibel. 


Umbilical  artery 
Bladder 


Symphysis  pubis 

Urogenital  sinus 


Genital  tubercle 
Urethra 


/-> 
—  Ovary 


.  Broad  ligament 
of  uterus 


—  Miillerian  duct 

—  Mesonephric  duct 
Ureter 


Recto-uterine 
excavation 


Rectum 


Tail 


FIG.  363. — From  a  reconstruction  of  the  caudal  end  of  a  human  embryo 

of  25  mm.  (8^-9  weeks).     Keibel. 
The  asterisk  (*)  indicates  the  urorectal  fold. 

ducts  open  near  the  external  orifice.     In  the  female  the  opening  of  the  develop- 
ing vagina  is  situated  on  the  dorsal  side  near  the  external  orifice. 

The  epithelium  of  the  prostate  gland  is  derived  by  evagination  from  the  proxi- 


406  TEXT-BOOK  OF  EMBRYOLOGY. 

mal  part  of  the  urethra.  The  first  evagination  appears  during  the  third  month. 
In  the  male  the  process  continues  to  form  a  rather  large  gland;  in  the  female  the 
structure  remains  in  a  rudimentary  condition.  During  the  fourth  month  two 
evaginations  arise  from  the  urethra  and  develop  into  the  bulbo-urethral 
(Cowper's)  glands  in  the  male,  into  the  larger  vestibular  (Bartholin's)  glands  in 
the  female. 

From  the  course  of  development  it  is  seen  that  the  epithelium  of  most  of  the 
bladder,  of  the  female  urethra  and  proximal  end  of  the  male  urethra,  of  the 


Germinal  &— -_  Stroma 

epithelium  — W^  '          (mesenchyme) 

(mesothelium) 


FIG.  364. — Transverse  section  through  the  germinal  epithelium  of  a  pig  embryo  of  1 1  mm.    Nagel. 

The  larger  cells  in  the  epithelium  represent  the  sex  cells,  the  smaller  ones  the 

undifferentiated  mesothelial  cells. 

prostate,  of  the  urogenital  sinus,  and  of  the  bulbo-urethral  and  vestibular 
glands  is  of  entodermal  origin.  A  very  small  part  of  the  bladder  epithelium 
is  of  mesodermal  origin,  since  the  proximal  ends  of  the  mesonephric  ducts, 
which  are  mesodermal  derivatives,  are  taken  up  into  the  wall.  All  the  connec- 
tive tissue  and  smooth  muscle  associated  with  these  organs  are  derived  from 
the  mesoderm  (mesenchyme)  which  surrounds  the  anlagen. 

THE  GENITAL  GLANDS. 
The  Germinal  Epithelium  and  Genital  Ridge. 

At  a  very  early  stage  in  the  formation  of  the  mesonephros,  a  narrow  strip 
of  mesothelium  extending  along  the  medial  surface  becomes  thicker  and  the 
cells  become  arranged  in  several  layers  (Figs.  314  and  346).  The  cells  become 
differentiated  into  two  kinds — (i)  small  cuboidal  cells  with  cytoplasm  which 
stains  rather  intensely,  and  (2)  larger  spherical  cells  with  clearer  cytoplasm  and 


THE   DEVELOPMENT   OF  THE   UROGENITAL  SYSTEM.  407 

large  vesicular  nuclei  (Fig.  364).  The  latter  are  the  sex  cells;  and  the  whole 
epithelial  (mesothelial)  band  is  known  as  the  germinal  epithelium.  The  sex 
cells  are  destined  to  give  rise  to  the  sexual  elements — in  the  female  to  the  ova, 
in  the  male  to  the  spermatozoa.  In  the  earlier  stages,  however,  it  is  impossible 
to  determine  whether  the  sex  cells  will  give  rise  to  male  or  female  elements. 
The  differentiation  of  sex  and  the  corresponding  histological  differentiation  of 
the  sex  cells  occur  at  a  later  period. 

In  his  recent  work  on  the  ovary  and  testis  in  Mammals,  Allen  has  ob- 
served in  very  early  stages  (pig  embryos  of  6  mm.,  rabbit  embryos  of  13  days) 
certain  large  cells,  with  large  clear  nuclei,  in  the  mesenchymal  tissue  of  the 
mesentery,  outside  of  the  genital  ridge.  These,  from  their  resemblance  to  the 
sex  cells  'within  the  genital  ridge,  should  probably  also  be  classed  as  sex  cells. 
Their  origin  in  these  animals,  however,  is  not  known  with  certainty;  but 
the  fact  that  in  turtle  embryos  Allen  has  found  cells  of  a  similar  character 
apparently  migrating  from  the  entoderm  through  the  mesoderm  to  the  site  of 
the  genital  glands  suggests  the  possibility  that  they  are  entodermal  derivatives. 
It  is  doubtful  whether  these  aberrant  sex  cells  take  part  in  the  development  of 
the  mature  sexual  elements,  the  latter  in  all  probability  being  derived  from 
the  sex  cells  of  the  mesothelium  of  the  genital  ridge. 

Beard,  Eigenmann,  Rabl,  Woods,  and  others,  have  described  sex  cells,  undoubtedly 
homologous  with  the  aberrant  sex  cells  mentioned  above,  as  occurring  in  various  regions  of 
the  embryos  of  certain  Fishes.  These  investigators  also  assert  that  the  sex  cells  become 
specialized  and,  so  to  speak,  segregated  at  a  very  early  period  of  development,  even  at  the 
stage  of  blastomere  formation.  Beard  contends  that  the  early  differentiated  sex  (or  germ) 
cells  are  significant  in  the  origin  of  certain  teratomata  (see  Chapter  on  Teratogenesis). 

The  cells  of  the  germinal  epithelium  increase  in  number  by  mitotic  division 
and,  for  some  time  at  least,  the  sex  cells  continue  to  increase  in  number  by 
differentiation  from  the  small  cuboidal  (indifferent)  cells,  as  indicated  by  the 
presence  of  intermediate  stages  between  the  two  types.  The  germinal  epi- 
thelium soon  becomes  separated  into  two  layers — (i)  a  superficial  layer  which 
retains  its  epithelial  character  and  contains  the  sex  cells,  and  (2)  a  deeper  layer 
composed  of  smaller  cells  which  resemble  those  of  the  mesenchyme  and  which 
give  rise  to  a  part,  at  least,  of  the  stroma  of  the  genital  glands.  The  elevation 
formed  by  these  two  layers  projects  into  the  body  cavity  from  the  medial  side 
of  the  mesonephros  and  constitutes  the  genital  ridge  (Fig.  346).  From  the 
superficial  epithelial  layer,  columns  or  cords  of  cells,  containing  some  of  the 
sex  cells,  grow  into  the  underlying  tissue.  This  ingrowth,  however,  does  not 
occur  equally  in  all  parts  of  the  genital  ridge,  for  three  fairly  distinct  regions 
can  be  recognized.  In  the  cephalic  end  comparatively  few  columns  appear, 
but  these  few  grow  far  down  into  the  underlying  tissue  and  constitute  the  rete 
cords.  In  the  middle  region  a  greater  number  of  columns  grow  into  the 


408 


TEXT-BOOK  OF  EMBRYOLOGY. 


stroma,  forming  the  sex  cords.  In  the  caudal  region  there  are  practically  no 
columns.  At  first  the  line  of  demarkation  between  the  cell  columns  and  the 
stroma  is  not  clearly  defined. 

The  changes  thus  far  described  are  common  to  both  sexes  and  are  completed 
during  the  fourth  or  fifth  week.  The  genital  ridges  or  anlagen  of  the  genital 
glands  constitute  "indifferent"  structures,  which  later  become  differentiated  into 
either  ovaries  or  testicles. 


Differentiation  of  the  Genital  Glands. 

After  the  fourth  or  fifth  week,  certain  changes  occur  in  the  genital  ridges 
which  differ  accordingly  as  the  ridges  form  ovaries  or  testicles.  While  the 
differences  are  at  first  not  particularly  obvious,  there  are  four  which  become 
clearer  as  the  changes  progress,  (i)  If  the  ridge  is  to  become  a  testicle,  the 
cells  of  the  surface  epithelium  become  arranged  in  a  single  layer  and  become 


Mesorchium 


Mesothelium 


Mesonephros 


Glomerulus 


Sex  cords 
(convoluted  semin- 
iferous tubules) 

FIG.  365. — Transverse  section  of  the  left  testicle  of  a  pig  embryo  of  62  mm.     Bonnet. 

fiat.     (2)  In  a  developing  testicle  a  layer  of  dense  connective  tissue  grows  be- 
tween the  surface  epithelium  and  the  sex  cords,  forming  the  tunica  albuginea. 

(3)  In  a  testicle  there  also  appears  a  sharper  line  of  demarkation  between  the 
cell  columns  and  the  stroma,  and  the  latter  shows  a  more  extensive  growth. 

(4)  Another  feature  of  the  testicle  is  that  the  sex  cells  begin  to  be  less  con- 
spicuous and  do  not  increase  further  in  size,  but  come  to  resemble  the  other 
epithelial  elements.     The  ovarian  characters  are  to  a  certain  extent  the  oppo- 
site,    (i)  The  surface  epithelium  does  not  become  flattened.     (2)  A  layer  of 
connective  tissue,  corresponding  to  the  albuginea  of  the  testicle,  grows  be- 


THE   DEVELOPMENT   OF  THE  UROGENITAL  SYSTEM. 


409 


tween  the  epithelium  and  the  deeper  parts,  but  is  of  a  looser  nature.  (3)  There 
is  a  less  sharp  line  of  demarkation  between  the  cell  columns  and  the  stroma. 
(4)  The  sex  cells  continue  to  increase  in  size  and  become  more  conspicuous. 
(Compare  Figs.  365  and  366.) 

During  these  processes  of  development,  the  anlage  of  each  genital  gland  be- 
comes more  or  less  constricted  from  the  mesonephros  and  finally  is  attached  only 
by  a  thin  sheet  of  tissue — the  mesovarium  in  the  female  or  the  mesorchium  in  the 


Oviduct 

(Ostium  abdom- 

inale  tubae) 


,-i Epoophoron 


Cortex 


•  *  -  •.    i  \    x  , 

-  v 

'•'    •'•'';'.-•-':    ' - •.4>^pxfi"W5  i?  Rete  cords 

.  j'^'^T'fv. (Reteovarii) 

& 


Medullary  cords 
(Medulla) 


vK- Mesonephros 


Oviduct 
FIG.  366. — Longitudinal  section  of  the  ovary  of  a  cat  embryo  of  94  mm.    Semidiagrammatic.    Coeri. 

male  (p.  423).     At  the  same  time  the  anlage  grows  more  rapidly  in  thickness 
than  in  length  and  assumes  an  oval  shape. 

The  Ovary. — As  stated  above,  a  layer  of  loose  connective  tissue,  correspond- 
ing to  the  albuginea  of  the  testicle,  grows  in  between  the  surface  epithelium  and 
the  cell  columns  (sex  cords)  and  effects  a  more  or  less  complete  separation. 
The  sex  cords  are  thus  pushed  farther  from  the  surface,  become  more  clearly 
marked  off  from  the  surrounding  stroma  and  constitute  the  so-called  medullary 
cords.  The  cortex  of  the  ovary  at  this  stage  is  represented  only  by  the  surface 
(germinal)  epithelium,  which  is  composed  of  several  layers  of  cells  and  contains 


.    «f       •_.  _  Mesovarium 


VX.'-V  •  -.*•/«.  •  f 

" 


Rete  ovarii 


FIG.  367.  —  Transverse  section  of  the  ovary  of  a  fox  embryo.     Biihler  in  Hertwig's  Handbuch. 
The  large  clear  cells  are  the  primitive  ova. 

some  of  the  cords  lumina  appear  and  are  lined  with  irregular  epithelium. 
Such  a  condition  represents  the  height  of  their  development  in  the  ovary. 
From  this  time  on,  they  degenerate  and  finally  disappear.  The  time  of  their 
disappearance  varies  in  different  individuals;  they  usually  persist  until  birth, 
sometimes  until  puberty. 

Formerly  it  was  thought  that  the  rete  cords  were  derived  from  the  meso- 
nephric  tubules  and  entered  the  genital  glands  secondarily.  More  recent  re- 
searches have  demonstrated  quite  conclusively,  however,  that  they  are  deriva- 
tives of  the  germinal  epithelium  and  unite  with  the  mesonephric  tubules 
secondarily. 

2  (a).  The  medullary  cords  are  composed  of  small  epithelial  cells,  contain  a 
number  of  larger  sex  cells  or  primitive  ova,  and  are  surrounded  by  stroma 
(Figs.  367,  368).  They  are  connected  with  the  rete  cords  and  in  some  places 
with  the  germinal  epithelium.  During  fcetal  life  they  give  rise  to  primary 
ovarian  (Graafian)  follicles;  later  they  degenerate  and  finally  disappear. 


410  TEXT-BOOK  OF  EMBRYOLOGY. 

numerous  sex  cells  in  various  stages  of  differentiation  (Fig.  367).  The 
rete  cords  which  arise  in  the  cranial  end  of  the  "indifferent"  gland  (p.  407) 
come  to  lie  in  what  will  be  the  hilus  of  the  ovary.  The  ovary  may  thus  be 
said  to  be  composed  of  two  parts — (i)  the  rete  anlage  and  (2)  the  stratum  ger- 
minativum.  The  latter  is  subdivided  by  the  albuginea  into  (a)  medulla  and 
(b)  cortex. 

i.  The  rete  cords  develop  into  a  group  of  anastomosing  trabeculae  which  con- 
stitute the  rete  ovarii,  situated  in  the  hilus  but  nearer  the  cephalic  end  of  the 
gland  (Fig.  366).  They  are  the  homologues  of  the  rete  testis.  The  cells  com- 
posing them  are  smaller  and  darker  than  those  of  the  medullary  cords.  Sprouts 
grow  out  from  the  rete  cords  and  unite  with  the  medullary  cords  and  the  meso- 
nephric  tubules.  (The  same  process  occurs  in  the  testicle,  where  the  rete  cords 
give  rise  to  the  functional  rete  testis  and  straight  seminiferous  tubules.)  In 


Cortex-     --^V.^V-V-VV',/  ^*'-V^  1 Mesothelium 

(Germinal  epithelium) 


Medulla  — 


THE   DEVELOPMENT   OF  THE   UROGENITAL  SYSTEM. 


411 


2(b).  The  cortex  of  the  ovary,  as  stated  above,  at  first  consists  of  several 
layers  of  small,  darkly  staining  cells,  among  which  are  many  large,  clearer  sex 
cells  or  primitive  ova  (Fig.  367).  From  the  epithelium,  masses  or  cords  of  cells 
grow  into  the  underlying  tissue,  carrying  with  them  some  of  the  primitive  ova. 
These  masses  are  known  as  Pftiiger's  egg  cords.  In  some  cases  several  ova  are 
grouped  together,  forming  egg  nests  (Fig.  368).  The  epithelial  cells  are  the 
progenitors  of  ihefollicular  cells  and  constantly  undergo  mitotic  division.  The 
primitive  ova,  on  the  other  hand,  increase  in  size  and  their  nuclei  show  distinct 
intranuclear  networks. 

The  egg  cords  become  separated  from  the  surface  epithelium  and  are 
broken  up  so  that  in  most  cases  a  single  ovum  is  surrounded  by  a  single  layer  of 


Germinal 
epithelium 


Corn- 

.    »£& 


• 


Medulla 


FIG.  368. — From  a  section  through  the  ovary  of  a  human  foetus  of  4  months.    Meyer-R&egg,  Buhler. 
The  large  cells  are  the  primitive  ova. 

)ithelial  cells.  This  constitutes  a  primary  Graafian  follicle.  Rarely  a  follicle 
contains  more  than  one  ovum.  In  the  case  of  the  egg  nests,  the  ova  may  become 
separated,  or  two  or  more  may  lie  in  one  follicle.  If  two  or  more  ova  are 
present  at  first  in  any  follicle,  usually  only  one  continues  to  develop  and  the 
others  either  degenerate  or  are  used  as  nutritive  materials.  In  very  rare  cases, 
however,  two  ova  may  develop  in  a  single  follicle,  but  whether  they  reach 
maturity  or  not  is  uncertain.  The  formation  of  egg  cords  is  usually  com- 
pleted before  birth,  but  in  some  cases  may  continue  for  one  or  twro  years  after 
birth.  During  the  processes  thus  far  described,  the  stroma  also  has  been  in- 
creasing, and  the  egg  cords  and  follicles  come  to  be  separated  by  a  considerable 
amount  of  connective  tissue.  The  germinal  epithelium  becomes  reduced  to  a 
single  layer  of  cuboidal  cells. 


412 


TEXT-BOOK  OF  EMBRYOLOGY. 


Each  primary  ovarian  follicle,  containing  a  primitive  ovum  (egg  cell,  sex  cell) , 
is  composed  of  a  single  layer  of  flat  or  cuboidal  cells,  plus  a  layer  of  stroma 
which  gives  rise  to  the  theca  folliculi.  As  the  ovum  continues  to  enlarge,  the 
follicular  cells  become  higher  and  arranged  in  a  radial  manner  (Fig.  369,  a) .  By 
proliferation,  the  follicular  cells  come  to  form  several  layers,  the  innermost 
layer  retaining  the  radial  character  and  forming  the  zona  radiata.  The  inner  or 
basal  ends  of  the  cells  of  the  zona  radiata  become  clear  to  form  the  zona  pellucida. 
In  the  latter,  radial  striations  appear  which  have  been  described  as  minute 


c  a 

FIG.  369. — Four  stages  in  the  development  of  the  ovarian  (Graafian)  follicle 

From  photographs  of  sections  of  a  cat's  ovary      Hertwig. 

The  ovum  is  not  shown  in  a,  b  and  c. 

channels  in  the  cells,  through  which  nutriment  may  pass  to  the  ovum.  After 
the  follicular  epithelium  has  become  several  layers  thick,  a  fluid  substance 
known  as  the  liquor  folliculi,  and  probably  derived  from  the  cells  themselves, 
comes  to  lie  in  little  pools  among  the  cells  (Fig.  369,  b  and  c ).  While  the  follicle 
as  a  whole  enlarges,  these  pools  gradually  coalesce  and  form  a  single  large  pool 
which  fills  the  interior  of  the  follicle  (Fib.  369,  d).  Thus  the  epithelium  is 
crowded  out  toward  the  periphery  where  it  forms  a  layer  several  cells  in  thick- 
ness, known  as  the  stratum  granulosum.  The  ovum  itself,  with  the  zona  radiata 
and  some  other  surrounding  cells,  is  also  crowded  off  to  the  periphery  of  the 


THE   DEVELOPMENT   OF  THE  UROGENITAL  SYSTEM.  413 

follicle.  The  little  elevation  of  the  stratum  granulosum  in  which  the  ovum 
is  embedded  is  known  as  the  cumulus  ovigerus  or  germ  hill  (see  Fig.  18). 

The  primary  ovarian  follicles  at  first  lie  rather  near  the  surface  of  the  ovary, 
but  as  they  enlarge  and  as  the  ovary  enlarges  they  come  to  lie  deeper.  As  the 
follicle  approaches  maturity  it  increases  greatly  in  size  (5  ±  mm.)  and  finally 
extends  through  the  entire  thickness  of  the  cortex,  its  theca  touching  the  tunica 
albuginea. 

In  speaking  of  the  development  of  the  follicles,  it  must  be  remembered  that 
they  develop  slowly  and  do  not  reach  maturity  until  near  the  age  of  puberty,  and 
furthermore  that  one,  or  very  few  at  most,  reach  maturity  at  the  same  time.  In 
other  words,  when  one  follicle  has  reached  maturity  there  are  all  intermediate 
stages  of  development  between  this  and  the  primitive  follicles.  When  a  follicle 
reaches  maturity  it  ruptures  at  the  surface  of  the  ovary  and  the  ovum  is  set  free 
(p.  31).  The  ovum  itself  undergoes  certain  changes  by  which  the  somatic 
number  of  chromosomes  is  reduced  one-half  (p.  17).  It  then  unites  with  the 
mature  spermatozoon,  which  also  contains  one-half  the  somatic  number  of 
chromosomes,  and  forms  the  starting  point,  so  to  speak,  for  a  new  individual. 
At  this  point  the  processes  by  which  an  individual  is  carried  through  its  life 
period  from  its  beginning  as  a  fertilized  ovum  to  the  time  when  it  produces  the 
next  generation  of  mature  sexual  elements  are  ended.  The  developmental 
cycle  of  one  generation  is  complete. 

It  has  been  estimated  that  approximately  36,000  primitive  ova  appear  in 
each  human  ovary.  Since,  as  a  rule,  only  one  ovum  escapes  from  the  ovary  at  a 
menstrual  period  or  between  two  succeeding  periods,  it  is  obvious  that  the  vast 
majority  of  these  never  reach  maturity.  They  probably  degenerate,  and,  as  a 
matter  of  fact,  atretic  follicles  may  be  found  in  an  ovary  at  any  time. 

CORPUS  LUTEUM. — After  the  rupture  of  the  mature  follicle  at  the  surface  of 
the  ovary  and  the  escape  of  the  ovum  and  liquor  folliculi,  blood  from  the  rup- 
tured vessels  fills  the  interior  of  the  follicle  and  forms  a  clot — the  corpus  hcemor- 
rhagicum.  The  cells  of  the  stratum  granulosum  proliferate  and  migrate  into 
the  clot  and  gradually  form  a  mass  which  replaces  the  blood.  It  is  held  by  some 
that  the  cells  are  derived  from  the  theca  folliculi.  Whatever  their  origin,  they 
become  infiltrated  with  a  fatty  substance  known  as  lutein.  Trabecuke  of 
connective  tissue  grow  into  the  mass  of  cells,  carrying  small  blood  vessels  with 
them.  The  (lutein)  cells  disintegrate  and  the  products  of  disintegration  are 
probably  carried  off  by  the  blood,  and  finally  the  entire  corpus  luteum  is  trans- 
formed into  a  mass  of  connective  tissue  (Figs.  19,  20  and  21,  and  p.  32). 

Whether  the  escaped  ovum  is  fertilized  or  not  has  an  influence  upon  the 
development  of  the  corpus  luteum.  In  case  of  fertilization,  the  corpus  luteum 
becomes  quite  large,  increasing  in  size  up  to  the  fourth  month  of  pregnancy,  and 
then  degenerates.  In  case  the  ovum  is  not  fertilized,  the  corpus  luteum  re- 


414  TEXT-BOOK  OF  EMBRYOLOGY. 

mains  smaller.     In  both  cases,  however,  the  histological  changes  are  essentially 
the  same  (p.  33). 

The  Testicle. — The  processes  that  give  rise  to  the  " indifferent "  genital 
glands  have  been  described  (p.  406  et  seq.} .  It  has  also  been  stated  that  there 
appears  during  the  fourth  or  fifth  week  a  structure  that  forms  one  of  the  char- 
acteristic features  of  the  testicle.  This  is  a  layer  of  dense  connective  tissue 
which  develops  beneath  the  surface  epithelium  and  constitutes  the  tunica 
albuginea  (p.  408),  and  which  separates  the  surface  epithelium  from  the  sex 
cords  (Fig.  365).  The  epithelium  becomes  reduced  to  a  single  layer  of  flat  cells, 
although  the  cells  on  the  tip  of  the  gland  usually  remain  high  until  after  birth. 
Naturally  this  epithelium  is  continuous  around  the  hilus  of  the  testicle  with  the 
epithelium  (mesothelium)  of  the  abdominal  cavity.  Within  the  gland  are  the 
sex  cords— the  progenitors  of  the  convoluted  seminiferous  tubules,  which  become 
quite  distinctly  marked  off  from  the  stroma  by  a  basement  membrane.  In  the 


Sex  cell 


Mesothelium    Tunica  Supporting  cell 

albuginea  (of  Sertoli) 

FIG.  370. — From  a  section  of  the  testicle  of  a  human  foetus  of  35  mm.,  showing  a  developing 
convoluted  seminiferous  tubule.     Meyer-Riiegg,  Bilhler. 

hilus  region  lie  the  rete  cords — the  progenitors  of  the  rete  testis  and  the  straight 
seminiferous  tubules  (Fig.  365) .  The  rete  cords  of  the  testicle  are  homologues  of 
the  rete  cords  of  the  ovary,  and  are  derivatives  of  the  germinal  epithelium  on  the 
cephalic  portion  of  the  "indifferent"  gland  (p.  407). 

The  s.ex  cords  at  first  are  solid  masses  composed  of  several  layers  of  cells. 
The  latter  are  of  two  kinds,  as  in  the  ovary — (i)  smaller,  darkly  staining  indiffer- 
ent cells,  and  (2)  larger,  clearer  sex  cells  (Fig.  370).  The  sex  cells  lose  their 
clearness  and  come  to  resemble  again  the  undifferentiated  epithelial  cells. 
They  represent  the  spermatogonia,  which  correspond  to  the  primitive  ova. 
The  spermatogonia  proliferate  very  rapidly  and  become  much  more  numerous 
than  the  epithelial  cells.  The  sex  cords  become  more  and  more  coiled  during 
development  and  anastomose  with  one  another  near  the  convex  surface 
of  the  testicle.  Beginning  after  birth  and  continuing  up  to  the  time  of 
puberty,  lumina  appear  in  them  by  displacement  of  the  central  cells,  and  I 


THE   DEVELOPMENT  OF  THE  UROGENITAL  SYSTEM.  415 

they  thus  give  rise  to  the  convoluted  seminiferous  tubules.  The  supporting 
cells  (of  Sertoli)  are  probably  derived  from  the  undifferentiated  epithelial  cells. 

The  details  of  the  further  development  of  the  spermatogonia  to  form  the 
the  spermatozoa  have  been  described  in  the  Chapter  on  Maturation.  At  this 
point,  that  is,  with  the  formation  of  the  spermatozoon,  the  life  cycle  from  a 
mature  male  sexual  element  in  an  individual  to  a  mature  male  sexual  element 
in  an  individual  of  the  succeeding  generation  is  completed. 

The  rete  cords  constitute  an  anastomosing  network  of  solid  cords  of  small, 
darkly  staining  cells,  situated  in  the  hilus  region.  These  cords  later  acquire 
irregular  lumina,  which  are  lined  with  cuboidal  cells,  and  form  the  rete  testis. 
Evaginations  grow  out  from  the  rete  and  fuse  with  the  ends  of  the  convoluted 
tubules,  thus  forming  the  straight  tubules.  On  the  other  hand,  outgrowths 
from  the  rete  unite  with  the  tubules  in  the  cephalic  portion  of  the  mesonephros, 
so  that  a  direct  communication  is  established  between  the  convoluted  semi- 
niferous tubules  and  the  mesonephric  tubules.  There  is  thus  formed  the  proxi- 
mal part  of  the  efferent  duct  system  of  the  testicle  (Fig.  365).  That  portion 
of  the  tunica  albuginea  in  which  the  rete  testis  lies,  becomes  somewhat  thickened 
to  form  the  mediastinum  testis. 

The  stroma  of  the  testicle  is  derived  for  the  most  part  from  the  mesenchyme 
of  the  "indifferent"  gland  or  genital  ridge.  Probably  a  smaller  part  is  derived 
from  the  germinal  epithelium  (see  p.  407).  During  development,  however, 
the  glandular  elements  increase  more  rapidly  than  the  stroma,  so  that  in  the 
adult  they  predominate.  There  is  a  tendency  for  the  convoluted  tubules  to 
become  arranged  in  groups  which  are  separated  by  trabeculae  of  connective 
tissue  radiating  from  the  mediastinum.  The  interstitial  cells  of  the  stroma  are 
direct  derivatives  of  the  connective  tissue  cells  (Fig.  370). 

Determination  of  Sex. 

The  question  of  the  determination  of  sex  has  caused  an  enormous  amount  of  speculation, 
and  has  been  the  subject  of  considerable  experimental  work.  The  speculation  has  led  to 
formulation  of  many  hypotheses,  some  of  which  have  been  in  part  corroborated  by  experiment 
and  observation,  others  of  which  are  hypotheses  pure  and  simple. 

The  hypotheses  may  be  divided  into  three  groups — according  to  which  the  determina- 
tion of  sex  is,  respectively,  progamous,  syngamous,  or  epigamous.  The  first  of  these  means 
that  the  sex  of  the  future  individual  is  determined  before  the  fertilization  of  the  ovum. 
The  differentiation  occurs,  according  to  some  authors,  in  the  ovum,  according  to  others, 
in  the  spermatozoon.  Syngamous  determination  means  that  the  differentiation  of  the 
sex  of  the  individual  occurs  at  the  time  of  fertilization.  According  to  the  hypotheses  of 
epigamous  determination,  the  fertilized  ovum  and  the  young  embryo  are  sexually  "indifferent," 
and  the  differentiation  of  sex  depends  upon  external  influences  acting  upon  the  embryo 
during  its  later  development. 

There  are  features  of  development  in  certain  forms  of  animals  in  favor  of  one  or  another 
of  these  groups  of  hypotheses.  For  example,  the  fact  that  in  one  of  the  Rotifers,  in  one  of  the 
27 


416  TEXT-BOOK  OF  EMBRYOLOGY. 


Worms,  and  in  one  of  the  plant  lice  two  forms  of  ova  ^are  produced,  the  larger  of  which 
always  develops  into  females  and  the  smaller  into  males,  is  evidence  in  favor  of  the  progam- 
ous  determination  of  sex.  In  the  rotifer  and  the  plant  louse  the  development  is  partheno- 
genetic  and  consequently  the  spermatozoa  can  have  no  influence.  Furthermore,  it  has  been 
shown  that  the  female  rotifer,  if  well  fed,  will  produce  only  the  larger  (female)  ova,  if  poorly 
fed,  only  the  smaller  (male)  ova.  The  most  remarkable  facts  in  favor  of  progamous  deter- 
mination of  sex  have  been  discovered  within  the  past  few  years  by  McClung,  Wilson,  Morgan, 
Correns  and  others.  These  investigators  have  demonstrated  variations  in  the  number  of 
chromosomes  in  many  species  of  Insects,  the  variation  being  constant  in  each  species.  In 
nearly  60  species,  Wilson  has  found  two  classes  of  spermatozoa,  differing  constantly  in  the 
number  of  their  chromosomes.  Morgan  has  shown  further  that  in  certain  forms  of  these  in- 
sects which  produce  a  series  of  parthenogenetic  generations,  the  fertilized  ova  produce 
females  only,  and  the  parthenogenetic  (non-fertilized)  ova  produce  both  males  and  females. 
He  has  also  shown  that  the  production  of  females  only  is  associated  with  the  fact  that  the 
spermatozoa  with  the  fewer  chromosomes  are  small  and  degenerate  without  reaching  ma- 
turity. This  leaves  only  one  kind  of  active  spermatozoa  that  unite  with  the  ova,  and  all  the 
fertilized  ova  produce  females.  In  regard  to  the  males  and  females  produced  without 
fertilization,  Morgan  has  made  the  discovery  that  the  somatic  cells  of  the  males  contain  only 
five  chromosomes,  whereas  those  of  the  females  contain  six. 

While  the  researches  were  at  first  carried  on  principally  with  Insects  they  have  more 
recently  included  a  number  of  other  animal  forms,  in  which  similar  variations  in  the] 
number  of  chromosomes  have  been  found  to  obtain.  From  this  and  from  the  fact  that 
Correns  found  a  like  variation  in  the  pollen  and  ova  of  certain  flowering  plants  it  may 
be  inferred  that  the  phenomenon  is  of  wide  occurrence. 

The  only  evidence  in  favor  of  syngamous  determination  of  sex  is  the  fact  than  in  bees  the 
fertilized  ova  develop  into  females,  the  unfertilized  (parthenogenetic)  ova  into  males.  Other 
experiments  and  observations  have  failed  to  throw  much  light  upon  any  possible  factors — 
such  as  the  relative  age  and  vigor  of  the  parents  or  the  relative  vigor  of  the  ova  and  sper- 
matozoa— in  this  type  of  determination. 

There  is  considerable  experimental  evidence  in  favor  of  epigamous  determination.  In 
experiments  where  accurate  observations  have  been  made,  it  appears  that  the  sex  of  the  indi- 
vidual depends,  to  some  extent  at  least,  upon  nutrition.  For  example,  a  brood  of  caterpillars 
was  divided  into  two  equal  lots.  In  the  period  preceding  the  pupa  stage,  one  lot  was  well  fed,  I 
the  other  lot  poorly  fed.  The  well  fed  lot  produced  sixty-eight  females  and  four  males; 
the  poorly  fed  lot  produced  seventy-six  males  and  three  females.  In  the  case  of  plant  lice,  I 
observations  show  that  during  the  summer  when  nutritive  conditions  are  most  favorable, 
females  only  are  produced;  that  in  the  autumn  when  the  weather  is  colder  and  the  food  con- 
ditions less  favorable,  both  males  and  females  are  produced.  In  experiments  on  tadpoles  the 
percentage  of  females  was  from  fifty-four  to  sixty-one  in  different  broods  of  unfed  animals;  in 
those  fed  with  beef  seventy-eight;  in  those  fed  with  fish,  eighty-one;  in  those  fed  with  frog 
meat,  ninety-two. 

Experiments  on  the  higher  animals  are  few,  but  it  appears  that  the  nutritional  conditions 
have  some  influence,  although  other  factors  of  importance  probably  enter  into  the  deter- 
mination of  sex.     Giron  divided  300  ewes  into  two  equal  groups.     One  group,  which  was 
well  fed  and  served  by  young  rams,  produced  sixty  per  cent,  of  female  offspring;  the  other 
group,  which  was  poorly  fed  and  served  by  older  rams,  produced  only  forty  per  cent,  of  female  ;  j 
offspring.     In  the  case  of  the  human  race  it  has  been  claimed  that  after  a  general  depression  in  i 
nutritional  conditions — such  as  war,  famine,  pestilence,  etc. — there  is   an  increased   pro- 
portion of  male  births. 


THE  DEVELOPMENT  OF  THE   UROGENITAL  SYSTEM. 


The  Ducts  of  the  Genital  Glands  and  the  Atrophy  of  the 
Mesonephroi. 

In  the  Female. — Strictly  speaking,  the  ovaries  are  ductless  glands;  for 
neither  developmentally  nor  anatomically  are  the  ducts  which  convey  their 
specific  secretion  directly  connected  with  them.  Furthermore,  these  ducts  are 
in  part  transformed  into  certain  organs  for  the  reception  and  retention  of  both 
kinds  of  sexual  elements.  In  other  words,  the  ducts  in  part  become  specially 
modified  to  form  the  vagina  and  uterus,  of  which  the  latter  serves  as  an  organ 
of  maintenance  for  the  embryos  of  the  next  generation. 

The  ducts  originate  in  connection  with  the  mesonephroi,  and  are  known  at 
first  as  the  Mullerian  ducts.  They  appear  in  both  sexes  alike  but  persist  only  in 
the  female.  In  the  lower  Vertebrates  they  are  split  off  from  the  mesonephric 
ducts.  In  the  higher  forms,  however,  their  mode  of  origin  is  not  known  with 


Ureter 


Intestine 


Mesonephric  duct 


Liver, 


Genital  cord 

Mullerian  duct 

Left  umbilical  artery 

Bladder 


Right  umbilical  artery 


FIG.  371. — From  a  transverse  section  through  the  pelvic  region  of  a  human  embryo 
of  25  mm.  (8^—9  weeks).     Keibel. 

-certainty,  but  the  present  evidence  favors  the  view  that  they  arise  independ- 
ently of  the  mesonephric  ducts.  They  appear  in  human  embryos  of  8-14  mm. 
The  mesothelium  on  the  lateral  surface  of  the  cephalic  end  of  each  mesonephros 
becomes  thickened  and  then  invaginates  or  dips  into  the  underlying  mesen- 
chyme.  By  proliferation  of  the  cells  at  its  tip,  the  invaginated  mass  grows 
caudally  as  a  duct  parallel  with  and  close  to  the  mesonephric  duct.  The  two 
ducts  come  to  be  embedded  in  a  ridge  which  at  the  cephalic  end  of  the  meso- 
nephros is  situated  laterally,  but  toward  the  caudal  end  bends  around  and  comes 
to  lie  ventrally.  Beyond  (caudal  to)  the  mesonephros  the  ridge  is  attached  to 
the  lateral  body  wall,  and  near  the  urogenital  sinus  it  meets  and  fuses  with  its 
fellow  of  the  opposite  side  (Fig.  371).  The  two  Mullerian  ducts,  contained 
in  the  ridges,  also  approach  each  other  and  fuse.  The  fusion  begins  in 
embryos  of  25  to  28  mm.  (end  of  second  month),  and  about  the  same  time  they 
open  into  the  dorsal  side  of  the  urogenital  sinus.  The  relations  of  the  Mullerian 


418  TEXT-BOOK  OF  EMBRYOLOGY. 

and  mesonephric  ducts  are  different  in  different  parts  of  their  courses.  At  the 
cephalic  end  the  Mullerian  lies  dorsal  to  the  mesonephric,  but  farther  back  it 
runs  more  laterally,  then  ventrally,  and  finally  opens  into  the  urogenital  sinus 
on  the  medial  side  of  the  mesonephric  duct. 

THE  OVIDUCT. — The  single  part  of  each  Mullerian  duct  gives  rise  to  the 
oviduct.  The  opening  at  the  cephalic  end  remains  as  the  ostmm  abdominale 
tub<z,  which  from  the  beginning  communicates  directly  with  the  abdominal 
cavity  (ccelom)  and  never  becomes  connected  with  the  ovary  (Fig.  366).  The 
rim  of  the  opening  sends  from  three  to  five  projections  into  the  abdominal 
cavity  to  form  the  primary  fimbrice.  Secondary  branches  grow  out  from  these 
and  form  the  numerous  fimbrias  of  the  adult  oviduct.  The  part  of  each 

Bladder 
"~~- —  i  -s^  Uterus        Rectum 


Cervix  uteri 


Symphysis  pubis 


Labium  majus  |      Hymen 

Labium  minus 

Vagina 

FIG.  372. — Right  half  of  the  pelvic  region  of  a  female  human  foetus  of  7  months.     Nagel. 

Miillerian  duct  between  the  fimbriated  end  and  the  fused  caudal  end,  grows  in 
length  as  the  embryo  develops,  but  not  proportionately,  so  that  in  the  adult  the 
oviduct  is  relatively  shorter  than  in  the  embryo.  At  first  it  is  lined  with  simple 
cylindrical  epithelium,  but  later  the  cells  become  cuboidal,  and  during  the 
second  half  of  foetal  life  acquire  distinct  cilia.  The  connective  tissue  and  muscle 
of  the  oviduct  are  derived  from  the  mesenchyme  that  primarily  surrounds  the 
Mullerian  duct. 

In  connection  with  one  of  the  fimbrise  of  the  oviduct  there  is  sometimes  found 
a  small  vesicle  lined  with  ciliated  epithelium,  forming  the  non-stalked  hydatid 
(of  Morgagni),  which  possibly  represents  the  extreme  cephalic  end  of  the 
Mullerian  duct  (Fig.  380).  In  this  case  the  permanent  ostium  of  the  tube 
would  be  of  secondary  origin. 


THE   DEVELOPMENT  OF  THE  UROGENITAL  SYSTEM.  419 

THE  UTERUS  AND  VAGINA. — The  fused  caudal  ends  of  the  two  Miillerian 
ducts  form  the  anlage  of  the  uterus  and  vagina,  which  is  a  single  medial  tube 
opening  into  the  urogenital  sinus  (Fig.  363).  During  the  third  month  certain 
histological  changes  bring  about  a  differentiation  between  the  cephalic  end  or 
uterus  and  the  caudal  end  or  vagina.  The  simple  columnar  epithelium  of  the 
vaginal  portion  changes  to  stratified  squamous,  and  during  the  fourth  month 
the  lumen  becomes  closed.  Near  the  external  orifice  a  semicircular  fold  ap- 
pears, which  represents  the  hymen  (Fig.  372).  During  the  sixth  month  the 
lumen  reappears  by  a  breaking  down  of  the  central  ceils.  The  epithelium  of 
the  uterus,  primarily  high  columnar,  becomes  lower  and  toward  the  end  of 
fetal  life  acquires  cilia.  Many  irregular  folds  appear  in  the  mucosa  of  the 
vagina,  a  smaller  number  in  the  uterus  (Fig.  372).  Some  of  the  folds  in  the 


g — Ovary 


Mesovarium 


Broad  ligament 
with  paroophoron 


Oviduct 


Mesosalpinx 
with  epoophoron 


FIG.  373. — Transverse  section  through  the  ovary  and  broad  ligament  of  a  human 
foetus  of  3  months.     Nagel. 

uterus  constitute  the  regular  plica  palmata  of  the  cervix.  The  uterine  glands 
represent  evaginations  from  the  epithelial  lining.  They  do  not  begin  to  develop 
until  after  birth  (one  to  five  years),  and  their  development  is  usually  not  com- 
pleted until  the  age  of  puberty. 

The  muscle  and  connective  tissue  of  the  walls  of  the  uterus  and  vagina  are 
derived  from  the  mesenchyme  which  surrounds  the  Miillerian  ducts.  The 
muscle  develops  relatively  late  (after  the  fourth  month  of  fcetal  life). 

ATROPHY  OF  THE  MESONEPHROI. — By  far  the  greater  part  of  each  meso- 
nephros  degenerates  and  disappears,  and  the  parts  that  do  persist  are  rudimentary 
and  possess  no  functional  significance.  The  cephalic  portion  leaves  ten  to 
twenty  coiled  tubules  which  terminate  blindly  at  one  end  and  at  the  other  end 
open  into  a  common  duct  that  represents  the  cephalic  end  of  the  mesonephric 
duct.  These  tubules  constitute  the  epoophoron  (parovarium,  organ  of  Rosen- 


420  TEXT-BOOK  OF  EMBRYOLOGY. 

miiller)  which  comes  to  lie  in  the  mesosalpinx  between  the  oviduct  and  the 
mesovarium,  and  later  in  the  mesentery  between  the  oviduct  and  the  ovary 
(Fig.  373).  At  the  height  of  their  development  the  tubules  are  lined  with 
columnar,  ciliated  epithelium.  The  rete  cords  of  the  ovary  (rete  ovarii,  p.  410) 
during  their  development  unite  with  the  tubules  in  the  cephalic  portion  of  the 
mesonephros,  but  later  disappear.  The  epoophoron  is  homologous  with  the 
tubules  of  the  head  of  the  epididymis  in  the  male. 

The  caudal  portion  of  the  mesonephros  leaves  a  ^ew  tubular  remnants 
which  come  to  lie  in  the  broad  ligament  near  the  hilus  of  the  ovary.  These  con- 
stitute the  paroophoron  \vhich  is  homologous  with  the  paradidymis  in  the  male 
(Fig.  373).  They  may  disappear  before  birth  or  may  persist  through  life. 

The  mesonephric  duct  also  leaves  certain  remnants  which  are  situated  (i)  in 
the  broad  ligament,  (2)  in  the  lateral  wall  of  the  uterus,  (3)  in  the  lateral  wall  of  the 
vagina,  and  (4)  in  the  tissue  lateral  to  the  external  genital  opening.  These  rem- 
nants are  known  as  the  canals  of  Gartner,  and  they  naturally  lie  in  the  course  of 
the  duct  in  the  embryo.  All  the  rudimentary  structures  derived  from  the 
mesonephroi  and  their  ducts  are  extremely  variable. 

In  the  Male. — In  the  male  all  the  efferent  ducts  of  the  genital  glands,  except 
the  rete  testis,  are  derived  from  the  mesonephroi  and  their  ducts.  As  described 
earlier  in  this  chapter  (p.  414),  the  rete  testis  acquires  a  connection  with  some  of 
the  tubules  in  the  cephalic  end  of  the  mesonephros  and  with  the  sex  cords  or 
anlagen  of  the  convoluted  and  straight  seminiferous  tubules  (see  Fig.  365). 
This  establishes  a  communication  between  the  seminiferous  tubules  and  the 
tubules  of  the  mesonephros.  Those  mesonephric  tubules  with  which  the  rete 
testis  unites  persist  as  the  efferent  ductules  (or  vasa  eff erentia) .  The  latter  form 
a  set  of  coiled  ducts  which  are  situated  in  the  head  of  the  epididymis  and  which 
open  into  the  cephalic  part  of  the  mesonephric  duct  (Fig.  347).  They  are 
homologous  with  the  epoophoron  in  the  female. 

The  next  succeeding  portion  of  the  mesonephric  duct  becomes  the  duct  of  the 
epididymis  which  in  its  tortuous  course  constitutes  the  bulk  of  the  body  and  tail 
of  the  epididymis  and  passes  over  into  the  caudal  portion  of  the  mesonephric 
duct.  The  latter  portion  becomes  the  deferent  duct  (vas  def erens) .  The  caudal 
end  of  the  deferent  duct  forms  the  ejaculatory  duct  which  opens  into  the  urogeni- 
tal  sinus.  The  seminal  vesicles  appear  during  the  third  month  as  lateral 
evaginations  from  the  ejaculatory  ducts. 

The  portions  of  the  mesonephros  not  involved  in  the  formation  of  the  duct 
system  of  the  testicle  atrophy  and  for  the  most  part  disappear.  They  leave 
certain  tubules,  however,  which  persist  as  rudimentary  structures  connected 
with  the  testicle.  In  the  cephalic  end,  some  of  the  tubules  persist  in  part  and 
come  to  lie  among  the  efferent  ductules,  being  either  attached  to  the  latter  or  un- 
connected, and  forming  the  appendage  of  the  epididymis.  The  caudal  part  of 


THE   DEVELOPMENT  OF  THE   UROGENITAL  SYSTEM. 


421 


the  mesonephros  leaves  a  few  tubules  which  come  to  lie  near  the  head  of  the  epi- 
didymis  and  form  the  paradidymis  (or  organ  of  Giraldes),  the  tubules  of  which 
are  lined  with  columnar,  ciliated  epithelium.  Near  the  transition  from  the 
duct  of  the  epididymis  to  the  deferent  duct  there  is  almost  invariably  a  tubule 
(sometimes  branched)  which  also  represents  a  remnant  of  the  mesonephros  and 
is  known  as  the  aberrant  ductule.  It  usually  opens  into  the  duct  of  the  epididy- 
mis, but  may  lie  free  in  the  tissue  around  it  (Fig.  347). 

ATROPHY  OF  THE  MULLERIAN  DUCTS. — These  ducts  persist  in  the  female 
and  become  the  oviducts,  uterus  and  vagina;  in  the  male  they  degenerate  and 
disappear  almost  entirely.  The  .degeneration  begins  about  the  time  they  open 


Diaphragmatic 
ligament  of 
mesonephros 


Genital  gland 


Mesonephros 


Mesoneohric  duct 


Urachus 


us-X 


Mesonephric  duct 


$- Inguinal  ligament 


Umbilical  artery 
FIG.  374. —  Urogenital  organs  in  a  human  embryo  of  17  mm.  (6  weeks).     Kollmann's  Atlas. 

into  the  urogenital  sinus  (embryos  of  25  to  28  mm.) ;  by  the  time  the  embryo 
reaches  a  length  of  60  mm.  only  the  extreme  cephalic  end  and  the  caudal 
third  remain,  and  at  90  mm.  the  entire  duct  is  gone  except  the  extreme  ends. 
The  cephalic  end  persists  as  the  appendix  testis  (or  hydatid  of  Morgagni) 
(Figs.  347,  379).  The  caudal  end  persists  as  the  utriculus  prostaticus  (uterus 
masculinus). 

Changes  in  the  Positions  of  the  Genital  Glands  and  the  Development 

of  their  Ligaments. 

During  the  early  stages  of  development  the  genital  glands — testicles  or 
ovaries — are  situated  far  forward  in  the  abdominal  cavity.  During  the  eighth 
week  they  lie  opposite  the  lumbar  vertebrae.  During  the  succeeding  months, 
up  to  the  time  of  birth,  they  gradually  move  caudally  to  the  positions  they 


422 


TEXT-BOOK  OF  EMBRYOLOGY. 


occupy  in  the  adult.  This  migration  is  brought  about,  to  some  extent  at 
least,  by  the  influence  of  certain  bands  of  tissue  which  are  primarily  like 
mesenteries.  As  the  mesonephros  develops  and  projects  into  the  body  cavity. 


Deferent  duct 

Inguinal  ligament 
(Gubernaculum  testis) 

Processus  vaginalis 
peritonaei 


Ureter 


Intestine 
Ureter 


FIG.  375. — From  a  dissection  of  the  pelvic  region  of  a  male  human  foetus  of  21  cm. 

Kollmann's  Atlas. 

it  comes  to  be  attached  along  the  dorsal  body  wall,  lateral  to  the  dorsal  mesen- 
tery, by  a  sheet  of  tissue  which  is  called  the  mesonephric  mesentery.  Cranial  to 
the  mesonephros,  this  mesentery  is  continued  as  the  diaphragmatic  ligament 


—  Spermatic  cord 
Inguinal  ring 


Tunica  vaginalis 

Testicle  and         \ 
epididymis 


Inguinal  cone 


Scrotum 


.Tunica  vaginalis 
communis 


Raphe" 


FIG.  376. — From  a  dissection  of  the  scrotal  region  of  a  human  fcetus  of  25  cm. 
Kollmann's  Atlas. 

of  the  mesonephros,  which  as  the  name  indicates,  is  attached  to  the  diaphragm; 
caudally  it  is  continued  to  the  inguinal  region  as  the  inguinal  ligament  of  the 


THE   DEVELOPMENT   OF  THE  UROGENITAL  SYSTEM. 


423 


mesonephros  (Fig.  374).  The  genital  gland  lies  on  the  medial  side  of  the 
mesonephros  and  is  attached  to  the  latter  by  a  sort  of  mesentery  which  becomes 
the  mesovarium  in  the  female  or  the  mesorchium  in  the  male.  The  cephalic 
portions  of  the  ducts  (Miillerian  and  mesonephric)  lie  close  together  in  a  ridge 
on  the  lateral  surface  of  the  mesonephros;  as  they  pass  caudally  they  extend 
around  to  the  ventral  surface  of  the  mesonephros  and  approach  the  medial  line, 
and  finally,  in  the  pelvic  region,  the  two  ridges  meet  and  fuse,  forming  the  so- 
called  genital  cord  (Fig.  371).  The  genital  cord  thus  contains  the  mesonephric 
and  Miillerian  ducts,  the  latter  fusing  to  form  a  single  tube  (the  anlage  of  the 
uterus  and  vagina,  p.  419).  It  also  contains  the  umbilical  arteries. 


Kidney 


Suprarenal  gland 


Intestine 


Round  ligament 
(Inguinal  ligament) 


Umbilical  artery 


Umbilical  vein 


FIG.  377. — From  a  dissection  of  the  pelvic  region  of  a  female  human  foetus  of  7.5  cm. 

Kollmann's  Atlas. 

Such  a  condition  is  found  in  embryos  of  about  eight  weeks.  From  this 
time  on,  the  processes  of  development  follow  divergent  lines  in  the  two  sexes, 
the  differences  becoming  more  marked  from  month  to  month.  Certain  struc- 
tures persist  and  other  disappear,  according  to  the  sex.  The  mesenteries  and 
ligaments  undergo  metamorphoses  and  the  genital  glands  migrate  caudally. 

Descent  of  the  Testicles. — As  the  mesonephros  atrophies,  its  mesentery 
and  the  mesentery  of  the  testicle  are  combined  to  form  a  single  band  of  tissue 
which,  of  course,  is  continuous  with  the  inguinal  ligament.  The  latter  now 
becomes  the  so-called  gubernaculum  testis  (Hunteri),  a  strong  band  or  cord 
composed  of  connective  tissue  and  smooth  muscle.  Its  cephalic  end  is  attached 
to  the  epididymis;  its  caudal  end  pierces  the  body  wall  in  the  inguinal  region  and 


424 


TEXT-BOOK  OF  EMBRYOLOGY. 


is  attached  to  the  corium  of  the  skin  (Fig.  375).  It  plays  an  important  part  in 
the  descent  of  the  testicle.  The  descent  is  brought  about  through  the  principle 
of  unequal  growth.  As  the  body  grows  in  length,  the  gubernaculum  grows 
much  less  rapidly  and,  since  the  caudal  end  of  the  latter  is  fixed,  the  natural 
result  is  the  drawing  downward  of  the  testicle.  This  takes  place  gradually, 
and  at  the  end  of  the  third  month  the  testicle  lies  in  the  false  pelvis ;  at  the  end 
of  the  sixth  month  close  to  the  body  wall  at  the  inguinal  ring. 

During  the  third  month  a  second  factor  in  the  descent  of  the  testicle  appears. 
This  is  an  evagination  of  the  peritoneum  at  the  point  where  the  gubernaculum 
pierces  the  body  wall.  The  evagination  at  first  is  a  shallow  depression,  known 


Kidney 

Mullerian  duct 

Genital  gland 
Mesonephros 


Ureter 


Inguinal  ligament 

Mesonephric  duct 

Mullerian  duct 


Apex  of  bladder 


Bladder 


Opening  of  ureter 


Opening  of  mesonephric  duct 

Opening  of  Mullerian  ducts 

Rectum 

Urogenital  sinus 

Cloaca 

Genital  tubercle 

Genital  ridge 

Opening  of  cloaca 


FIG.  378. — Diagrammatic  representation  of  the  urogenital  organs  in  the  "  indifferent  "  stage.  Hertiuig. 


as  the  processus  vaginalis  peritonei,  but  continues  to  burrow  through  the  body 
wall  and  causes  an  elevation  in  the  skin  which  is  destined  to  become  one  side  of 
the  scrotum  (see  p.  430) .  The  opening  of  the  peritoneal  sac  into  the  body  cavity 
is  the  inguinal  ring.  In  its  descent  the  testicle  passes  through  the  inguinal  ring 
and  comes  to  lie  in  the  elevation  in  the  skin  or  scrotum  (ninth  month) .  Whether 
its  passage  into  the  scrotum  is  the  result  of  a  traction  by  the  gubernaculum  is 
not  certain.  The  inguinal  ring  then  closes  by  apposition  of  its  walls  and  the 
testicle  lies  in  a  closed  sac  which  has  been  pinched  off,  so  to  speak,  from  the  body 
cavity  (Fig.  376). 


THE   DEVELOPMENT  OF  THE   UROGEXITAL  SYSTEM. 


425 


Kidney 

Appendage  of  testicle 
(hydatid  of  Morgagni) 

Epididymis 

Testicle 

Paradidymis 

Deferent  duct 

Mullerian  duct 

Gubernaculum  testis 

Ureter 

Seminal  vesicle 
Deferent  duct 


Epididymis 
Testicle 

Gubernaculum  testis 


Kidney 


Hydatid 

Oviduct 
(fimbriae) 

Epoophoron 
Ovary 

Paroophoron 
Mesonephric  duct 

Oviduct 
Epoophoron 

Ovary 
Ovarian  ligament 

Uterus 
Round  ligament 


Vagina 


Urethra    Sinus  prostaticus 

FIG.  379. 


Apex  of  bladder 


Bladder 


Opening  of  ureter 

Urethra 

Opening  of  ejacul.  duct 

Prostate 


Apex  of  bladder 


Urethra 
Vestibulum  vaginae 


FIG.  380. 

FIG.  379. — Diagram  of  the  development  of  the  male  genital  organs  from  the 

"indifferent"  anlagen.     Hertwig. 
FIG.  380. — Diagram  of  the  development  of  the  female  genital  organs  from  the 

"  indifferent "  anlagen.     Hertwig. 
These  diagrams  should  be  compared  with  Fig.  378.     The  dotted  lines  represent  the  organs  in  the 
relative  positions  they  occupy  in  the  adult  (with  the  exception  of  the  Miillerian  duct  in  the 
male  and  the  mesonephric  duct  in  the  female,  which  ducts  disappear  for  the  most  part). 


426  TEXT-BOOK  OF  EMBRYOLOGY. 

Since  the  testicle  is  invested  by  peritoneum  from  the  beginning  of  its  develop- 
ment, it  must  be  understood  that  in  its  passage  into  the  scrotum  it  passes  along 
under  the  peritoneum.  Consequently  when  it  reaches  the  scrotum  it  is  sur- 
rounded by  a  double  layer  of  peritoneum,  the  tunica  vaginalis  propria. 

The  descent  of  the  testicle  also  produces  marked  changes  in  the  course  of 
the  deferent  duct.  Primarily  the  (mesonephric)  duct  extends  cranially  from 
the  urogenital  sinus  in  a  longitudinal  direction.  But  as  the  testicle  migrates, 
the  cephalic  end  of  the  duct  is  drawn  caudally  so  that  in  the  adult  the  deferent 
duct  extends  cranially  from  the  scrotum  to  the  ventral  side  of  the  urinary 
bladder  and  then  bends  caudally  again  to  open  into  the  urethra. 

Descent  of  the  Ovaries. — The  ovaries  undergo  a  change  of  position  cor- 
responding to  the  descent  of  the  testicles,  although  the  change  is  not  so  extensive. 
Primarily  the  Miillerian  and  mesonephric  ducts  lie  in  a  ridge  on  the  surface  of 
the  mesonephros  (p.  417).  As  the  mesonephros  and  its  duct  atrophy,  the  Miil- 
lerian duct  (oviduct)  comes  to  lie  in  a  fold,  the  mesosalpinx,  which  is  attached 
to  the  mesovarium  (Fig.  373) .  At  the  same  time  the  mesovarium  becomes  directly 
continuous  with  and  really  a  part  of  the  inguinal  ligament.  The  latter  cor- 
responds, of  course,  to  the  gubernaculum  testis,  and  plays  a  role  in  the  descent 
of  the  ovaries.  It  may  be  conveniently  divided  into  three  parts,  (i)  a  cephalic 
part  which  is  attached  to  the  hilus  of  the  ovary,  (2)  a  middle  part  which  ex- 
tends from  the  ovary  to  the  uterus,  forming  the  ovarian  ligament,  and  (3)  a  cau- 
dal part  which  extends  from  the  uterus  to  the  inguinal  region,  forming  the 
round  ligament  of  the  uterus  (Fig.  377).  The  round  ligament  pierces  the  body 
wall  and  is  attached  to  the  corium  of  the  skin.  At  the  point  where  it  passes 
through  the  body  wall  there  is  a  slight  evagination  of  the  peritoneum,  the 
diverticulum  of  Nuck,  which  corresponds  to  the  processus  vaginalis  peritonei 
in  the  male. 

The  ovaries  gradually  migrate  caudally  from  their  original  position  into  the 
false  pelvis  (third  month)  and  thence  into  the  true  pelvis  (at  birth).  Obviously 
no  traction  can  be  exerted  upon  them  by  the  round  ligament  (or  caudal  part  of 
the  inguinal  ligament),  since  the  latter  extends  from  the  uterus  to  the  inguinal 
region.  Their  descent  into  the  pelvic  seems  to  be  due  to  the  unequal  growth 
of  the  ovarian  ligaments,  or  in  other  words,  to  the  fact  that  the  ovarian  liga- 
ments grow  proportionally  less  than  the  surrounding  parts.  During  their 
descent  the  ovaries  become  embedded  in  the  broad  ligaments  of  the  uterus, 
which  represent  further  development  of  the  peritoneal  folds  of  the  genital  cord. 
In  this  way  the  mesovarium  becomes  merged  with  the  broad  ligament. 

On  pages424  and  425  are  three  diagrammatic  representations  of  the  changes 
that  take  place  in  the  genital  systems  of  the  two  sexes.  Fig.  378  represents 
the  "indifferent"  stage  in  which  all  the  embryonic  structures  are  present; 
Fig.  379  represents  the  changes  that  occur  in  the  male;  Fig.  380  represents  the 


THE   DEVELOPMENT   OF  THE  UROGENITAL  SYSTEM. 


427 


changes  that  occur  in  the  female.  A  careful  study  of  the  diagrams  will  assist 
the  student  materially  in  understanding  the  processes  of  development  which 
have  been  described  in  the  preceding  paragraphs. 

Below  is  a  table  that  is  meant  to  set  forth  briefly  the  various  structures 
which  belong  to  the  internal  genital  organs  in  the  two  sexes,  and  which  are 
derived  from  the  structures  in  the  "indifferent"  stage.  The  words  in  italics- 
are  the  names  of  structures  that  persist  in  a  rudimentary  form. 


Indifferent 


Male 


Female 


Germinal  epithelium  (meso- 
thelium) 


Convoluted  seminiferous  tubules  1 

with  spermatozoa J 

Straight  seminiferous  tubules  . 

Rete  testis 

Part  of  stroma  of  testicle 


Ovarian   (Graafian)  follicles 
with  ova. 

Medullary  cords 

Rete  cords. 

Part  of  stroma  of  ovarv. 


Mesonephros 


f  cephalic  part 
[  caudal  part 


Efferent  ductules  (vasa  efferentia)  \ 
A  ppendagc  of  epididymis  .  .  .  / 
Paradidymis  (organ  of  Giraldes)  \ 
Aberrant ductules(vasa aberrantia)  J 


Epoophoron,  transverse  duc- 
tules. 

Paroophoron. 


Mesonephric  duct      .... 


Mullerian  duct 


Duct  of  epididymis  (vas  epididy- 

midis)      

Deferent  duct  (vas  deferens)  .    . 

Ejaculatory  duct 

Seminal  vesicle  . 


Vesicular     appendage     (of 

Morgagni)  (?) 
\  Epoophoron,       longitudinal 

duct. 
[  Gartner's  canals. 


Inguinal  ligament  of   meso- 
nephros   . 


Morgagni's  appendage  of  testicle  \ 
(hydatid  of  Morgagni)      .    .    .   J 


Prostatic  utricle  (uterus  masculinus) 
Gubernaculum  testis  (Hunteri)  .    . 


Fimbriae  of  oviduct 

Oviduct. 

Uterus. 

Vagina. 


Urogenital  sinus 


Urethra  ^  pr°static  part  '    '    •    • 
\  membranous  part    .    . 

Prostate 

Bulbo-urethral  gland  (Cowpers) 


f  Ovarian  ligament. 

\  Round  ligament  of  uterus. 

/  Urethra. 

\  Vestibule  of  vagina. 
Prostate. 

Larger  vestib alar  gland  (Bar- 
tholin's. 


THE  EXTERNAL  GENITAL  ORGANS. 

In  addition  to  the  internal  organs  of  generation,  to  which  the  description  has 
thus  far  been  confined,  certain  other  structures  appear  on  the  outside  of  the 
body  to  form  the  external  genitalia.  In  the  case  of  these  also  there  is  an  "  indif- 
ferent" stage  from  which  the  courses  of  development  diverge  in  the  two  sexes. 

During  the  sixth  week  a  depression  appearing  on  the  ventral  surface  of  the 
caudal  end  of  the  body  indicates  the  position  of  the  cloacal  membrane  (p.  403) . 
This  becomes  surrounded  by  a  slight  elevation,  produced  by  the  thickening 
of  the  mesoderm  which  is  known  as  the  genital  ridge  (Fig.  381).  The  cephalic 


428  TEXT-BOOK  OF  EMBRYOLOGY. 

side  of  the  ridge  becomes  raised  still  farther  above  the  surface,  forming  a  dis- 
tinct protrusion,  the  genital  tubercle.  The  tubercle  continues  to  increase  in 
size,  and  the  distal  end  forms  a  knob-like  enlargement.  Along  the  ventral  (or 
rather  caudal)  side  a  groove  appears,  which  extends  distally  as  far  as  the  base 
of  the  enlarged  end.  The  ridges  along  the  sides  of  the  groove  increase  in 
size  and  form  the  genital  folds.  In  the  meantime  a  second  pair  of  elevations 
appears  lateral  to  the  genital  folds  to  form  the  genital  swellings  (Fig.  382). 

After  the  cloacal  membrane  ruptures,  a  single  opening  is  produced  which 
leads  from  the  exterior  into  the  cloaca.  This  opening  is  then  separated  by  the 
further  growth  of  the  urorectal  fold  (p.  403)  into  the  opening  of  the  urogenital 
tract  and  the  anal  opening.  The  caudal  part  of  the  fold  then  enlarges  to  form 
the  perineal  body,  which  serves  to  push  the  anus  farther  away  from  the  genital 
ridges.  The  latter,  together  with  the  genital  tubercle  and  swellings,  all  of  which 
lie  in  the  immediate  vicinity  of  the  urogenital  opening,  constitute  the  anlagen 
of  the  external  genital  organs  (Fig.  383).  These  at  this  time  are  in  the 
"indifferent"  stage,  from  which  development  proceeds  in  one  of  two  directions, 
accordingly  as  the  embryo  is  a  male  or  a  female.  Up  to  the  fourth  month 
there  is  little  difference  between  the  structures  in  the  two  sexes.  After  this  the 
differences  become  more  and  more  obvious. 

In  the  female  the  changes  in  the  originally  "indifferent"  structures  are 
comparatively  slight.  The  genital  tubercle  grows  slowly  and  becomes  the 
clitoris.  The  enlarged  extremity  becomes  more  clearly  marked  off  from  the 
other  part  to  form  the  glans  clitoridis.  The  skin  covering  the  glans  is  converted 
by  a  process  of  folding  into  a  sort  of  prepuce.  The  genital  folds,  which 
bound  the  opening  of  the  urogenital  tract,  become  elongated  and  form  the 
labia  minora.  The  opening  of  the  urogenital  tract  is  the  vestibulum  vagina. 
The  genital  swellings  enlarge  still  more  than  the  genital  folds,  by  a  deposition 
of  a  considerable  mass  of  fat  in  the  mesenchyme,  and  become  the  labia  majora. 
The  latter  are  the  structures  (mentioned  on  p.  424)  which  mark  the  points 
at  which  the  inguinal  ligaments  of  the  mesonephroi  pierce  the  body  wall,  and 
are  homologous  with  the  scrotum  in  the  male  (Figs.  384  and  385). 

In  the  male  the  "indifferent"  anlagen  undergo  more  extensive  changes 
than  in  the  female.  The  genital  tubercle  continues  to  grow  more  rapidly  and 
forms  the  penis,  which  is  homologous  with  the  clitoris.  The  enlarged  extremity 
becomes  the  glans  penis,  and  an  extensive  folding  of  the  skin  over  the  glans 
forms  the  prepuce.  The  groove  on  the  caudal  or  lower  side  of  the  tubercle 
elongates  as  the  latter  elongates  and  becomes  deeper.  Finally  the  ridge  (or 
genital  fold)  on  each  side  of  the  groove  meets  and  fuses  with  its  fellow  of  the 
opposite  side,  thus  enclosing  within  the  penis  a  canal — the  penile  portion  of 
the  urethra.  The  groove  is  primarily  continuous  with  the  opening  of  the  uro- 
genital tract,  and  as  the  fusion  takes  place  the  penile  portion  forms  a  direct 


Gen.  r. 


THE   DEVELOPMENT   OF  THE   UROGENITAL  SYSTEM.  429 

Umb.  c. 


fP3-   Umb.  c. 


-   Gen.  tub. 


Gen.  f. 


Ug.  s.   - 


FIG.  385.  FIG.  386. 

FIGS.  381-386. — Stages  in  the  development  of  the  external  genital  organs.     Kollmann's  Atlas. 
FIG.  381,  "  indifferent  "  stage — embryo  of  17  mm.;  Fig.  382,  "  indifferent  "  stage — embryo  of  23  mm.; 

Fig.  383,  "indifferent"  stage — embryo  of  29  mm.  (beginning  of  3d  month);  Fig.  384,  female 

embryo  of  70  mm.  (u  weeks);  Fig.  385,  female  embryo  of  150  mm.  (16  weeks);  Fig.  386, 

male  embryo  of  145  mm.  (16  weeks). 
An.,  Anus;  CL,  clitoris;  Clo.  and  gen.  /.,  cloaca  and  genital  folds;  Cl.  in.,  cloacal  membrane;  Ext., 

lower  extremity;    Gen.  /.,  genital  folds;  Gen.  r.,  genital  ridge;    Gen.  su'.,  genital  swelling; 

Gen.  tub.,  genital  tubercle;  Gl.  p.,  glans  penis;  Lab.  ma.,  labium  majus;  Lab.  mi.,  labium 

minus;    Ra.,  raphe  of  scrotum;  \Scr.,  scrotum;  Ta.,  tail;   Ug.  s.,  urogenital  sinus;   Umb.  c.y 

umbilical  cord. 


430  TEXT-BOOK  OF  EMBRYOLOGY. 

continuation  of  the  internal  (membranous  and  prostatic)  portion  of  the  urethra. 
The  genital  swellings  also  fuse  and  form  the  scrotum,  the  line  of  fusion  in  the 
medial  line  becoming  the  raphe  (Fig.  386).  Primarily  the  inguinal  ligaments 
of  the  mesonephroi  are  attached  to  the  corium  of  the  skin  in  the  genital  swellings, 
and  as  the  testicles  descend  they  pass  through  the  inguinal  ring  into  the  scro- 
tum. In  a  sense  the  scrotum  represents  an  evagination  of  the  body  wall 

THE  DEVELOPMENT  OF  THE  SUPRARENAL  GLANDS. 

Although  the  suprarenal  glands  do  not  logically  come  under  the  head  of  the 
urogenital  system,  being  neither  functionally  nor  developmentally  a  part  of  the 
latter,  it  is  most  convenient  to  consider  them  in  this  chapter. 

In  Mammals  including  man  these  glands  are  composed  of  two  parts  which 
can  be  differentiated  histologically  and  topographically — the  cortex  and 
medulla.  The  cortex  is  composed  of  trabeculse  and  spheroidal  masses  of  cells 

Phaeochrome  cells 


Nerve  fibers 


Phaeochrome    Connective  Sympathetic 

cells  tissue  ganglion  cells 

FIG.  387. — Section  of  a  sympathetic  ganglion  in  the  cceliac  region  of  a  frog  (Rana  esculenta), 
showing  differentiating  pha^ochrome  cells.     Giacomini. 

which  do  not  have  a  strong  affinity  for  the  ordinary  cytoplasmic  stains  and 
which  contain  granules  of  a  fat-like  substance  known  as  lipoid  granules.  The 
medulla  is  composed  of  irregularly  arranged  sympathetic  ganglion  cells  and 
other  granular  cells  which,  after  treatment  with  chrome  salts,  acquire  a  peculiar 
brownish  color.  The  brown  cells  are  known  as  chromaffin  (or  phseochrome) 
cells  and  their  granules  as  chromaffin  (or  phseochrome)  granules.  As  cortex 
and  medulla  are  distinct  anatomically,  they  are  also  distinct  developmentally, 
being  derived  from  two  distinct  and  different  parent  tissues  which  unite 
secondarily.  Furthermore,  it  is  an  interesting  fact  that  in  the  lower  Vertebrates 
(Fishes)  the  two  parts  remain  permanently  separate;  that  in  the  ascending 
scale  of  animal  life  (Amphibia,  Reptiles,  Birds)  they  become  more  closely 
associated;  and  that  finally  (in  Mammals)  they  unite  to  form  a  single  glandular 
structure.  In  Mammals  the  phylogenetic  history  is  repeated  with  remarkable 


THE   DEVELOPMENT  OF  THE   UROGENITAL  SYSTEM. 


431 


precision  during  the  development  of  an  individual :  The  two  parts  arise  sepa- 
rately, come  closer  together,  and  finally  unite. 

The  Cortical  Substance.— The  cortex  is  of  mesothelial  (mesodermal) 
origin.  In  embryos  of  five  to  six  mm.  the  mesothelium  at  the  level  of  the 
cephalic  third  of  the  mesonephros  proliferates  and  sends  buds  or  sprouts  into 
the  mesenchyme  at  each  side  of  the  root  of  the  dorsal  mesentery.  These 
sprouts  soon  lose  their  connection  with  the  parent  mesothelium  and  unite  with 
one  another  to  form  a  rather  compact  mass  of  epithelial-like  cells  ventro-lateral 
to  the  aorta  (Fig.  314).  Frequently  the  two  masses  fuse  across  the  medial  line 
ventral  to  the  aorta.  They  constitute  the  anlagen  of  the  cortical  substance  of 


Cortex 
Connective  tissue 


Medulla   — 18 
Cortex 


Cortex 


Medulla 
(Phseochrome  cells) 


FIG.  388. — From  a  transverse  section  of  a  40  mm.  pig  embryo,  showing  the  growth  of  the  medullary 
substance  into  the  cortical  substance  of  the  suprarenal  gland.  The  vessel  in  the  center  of 
the  figure  is  the  aorta.  Wiessl. 

the  two  suprarenal  glands.  From  the  fact  that  in  the  lower  forms  they  remain 
separate  from  the  medullary  substance  and  lie  between  the  urinary  organs, 
they  are  known  as  the  interrenal  organs. 

The  Medullary  Substance. — A  little  later  than  the  appearance  of  the 
cortical  anlage,  the  cells  of  some  of  the  developing  sympathetic  ganglia  become 
differentiated  into  two  types — (i)  the  so-called  sympathoblasts  which  develop  into 
sympathetic  ganglion  cells,  and  (2)  phaochromoblasts  which  are  destined  to  give 
rise  to  the  phaeochome  or  chromaffin  cells  (Fig.  387).  Hence  the  chromafnn 
cells  are  derivatives  of  the  ectoderm,  since  the  ganglia  are  of  ectodermal  origin. 
They  soon  become  more  or  less  separated  from  the  ganglia,  migrate  to  the 
28 


432 


TEXT-BOOK  OF  EMBRYOLOGY. 


region  of  the  cortical  anlagen  and  then  penetrate  the  latter  in  cord-like  masses 
(Fig.  388) .  Finally  these  masses  unite  in  the  interior  of  the  cortical  substance 
to  form  a  single  compact  mass  (Fig.  389).  Along  with  the  phaeochrome  masses, 
sympathoblasts  also  are  carried  in  and  give  rise  to  the  sympathetic  ganglion  cells 
within  the  gland.  The  two  types  of  cells  together  constitute  the  medullary 
substance.  In  the  lower  forms  the  phseochrome  masses  remain  separate  from 
the  cortical  substance  and  are  known  as  the  suprarenal  organs.  In  Mammals 
the  two  sets  of  organs  (interrenal  and  suprarenal)  unite  to  form  the  suprarenal 
gland. 


Med.    Cor.    Cor.1 


FIG.  389. — Section  of  the  suprarenal  gland  of  a  119  mm.  pig  embryo.     Cor.,  Cortex;  Cor.1,  some 
cortical  substance  in  the  center  of  the  gland;  Med.,  medulla.     Wiesel. 

At  the  time  when  the  mesonephros  is  fully  developed,  the  cortical  substance 
forms  a  small  oval  body  near  its  cephalic  end.  During  the  union  of  the  cortex 
and  medulla  and  the  atrophy  of  the  mesonephros,  the  suprarenal  gland  becomes 
more  closely  associated  with  the  cephalic  end  of  the  kidney,  and  by  the  middle  of 
the  third  month  has  practically  reached  its  adult  position.  During  the  third 
month  and  the  first  half  of  the  fourth  month  the  glands  increase  in  size  and 
become  relatively  large  structures,  larger  in  fact  than  the  kidneys.  From  the 
fourth  month  on,  they  grow  proportionately  less  than  the  neighboring  organs, 
and  by  the  sixth  month  are  about  half  as  large  as  the  kidneys.  At  birth  the 
ratio  of  their  weight  to  that  of  the  kidneys  is  about  1:3;  in  the  adult  about  i :  28. 

While  perhaps  in  a  normal  course  of  development  all  the  anlagen  are  united 
in  the  adult  suprarenal  gland,  it  is  not  unusual  to  find  accessory  structures  in 
various  places.  Some  of  these  consist  of  cortical  tissue  only  and  are  usually 


THE   DEVELOPMENT   OF  THE   UROGENITAL  SYSTEM. 


433 


found  in  or  near  the  capsule  of  the  gland.  Others  may  consist  of  both  cortical 
and  medullary  substances,  and  are  found  in  the  vicinity  of  or  embedded  in  the 
kidneys,  in  the  retroperitoneal  tissue  near  the  kidneys,  in  the  walls  of  neighbor- 
ing blood  vessels,  or  associated  with  the  internal  genital 
organs — in  the  rete  testis  or  epididymis,  or  in  the  broad 
ligament.  These  accessory  structures  may  arise  inde- 
pendently of  the  main  gland,  or  they  may  be  portions  of 
the  main  gland  which  were  separated  during  the  union 
of  the  different  anlagen  of  the  latter  and  were  carried 
away  in  the  descent  of  the  genital  glands. 

In  addition  to  the  chromaffin  tissue  which  enters  into 
the  formation  of  the  main  gland  or  of  accessory  glands, 
there  are  other  small  masses  of  this  tissue  which  remain 
permanently  associated  with  some  of  the  prevertebral 
and  peripheral  sympathetic  ganglia. 

Recent  researches  have  shown  that  the  Carotid  Skein 
(glomus  caroticum,  intercarotid  ganglion,  carotid  gland), 
which  formerly  was  believed  to  be  a  derivative  of  the 
epithelial  lining  of  one  of  the  branchial  grooves,  is  of 
sympathetic  origin  and  that  the  cells  acquire  the  charac- 
teristic chromaffin  reaction.  These  facts  indicate  that 
it  is  closely  allied  with  the  medullary  substance  of  the  suprarenal  gland. 


•.n 

FIG.  390. — Diagram  of 
the  developing  phaeo- 
chrome  masses  in  a 
human  fretus  of  50 
mm.  A,  Aorta;  Nf 
cortical  substance  (in- 
terrenal  gland) ;  U, 
ureter;  R,  rectum. 
Kohn. 


Anomalies. 

THE  KIDNEYS. — Rarely  is  there  congenital  absence  of  both  kidneys.  More 
often  there  is  a  high  degree  of  aplasia  in  both  organs  in  otherwise  well-developed 
children.  In  either  case  death  necessarily  soon  follows.  Not  infrequently  one 
kidney,  usually  the  left,  is  poorly  developed  or  absent  and  a  compensatory 
enlargement  of  the  other  exists.  Such  malformations  are  due  to  deficient 
development  of  the  organs,  but  the  causes  underlying  the  deficient  development 
are  obscure. 

One  of  the  most  common  malformations  is  the  abnormal  position  of  one  or 
both  kidneys  (ectopia  of  the  kidneys).  Usually  they  occupy  a  position  lower 
than  the  normal  in  the  abdominal  cavity,  which  indicates  that  they  have  failed, 
during  development,  to  migrate  forward  to  the  normal  limit  (see  p.  402) .  Very 
rarely  one  or  both  organs  migrate  beyond  the  normal  limit,  in  which  case  they 
occupy  positions  cranial  to  the  normal. 

Not  infrequently  the  lower  ends  of  the  two  kidneys  are  fused  across  the 
medial  line,  giving  rise  to  the  so-called  "horseshoe  kidney."  Two  renal 
pelves  and  ureters  are  usually  present.  Occasionally  the  fusion  is  so  extensive 


434  TEXT-BOOK  OF  EMBRYOLOGY. 

that  a  single  flat  mass  is  formed.  This  occupies  a  medial  position  or  lies  at 
either  side  of  the  medial  line,  and  may  be  situated  at  the  normal  level  or  lower. 
The  renal  pelvis  may  be  single  or  double,  with  one  or  two  ureters.  In  cases  of 
double  ureters  and  pelves  it  seems  most  likely  that  the  anlagen  of  the  kidneys 
have  fused  secondarily,  that  is,  after  the  evagination  from  the  mesonephric 
ducts  (p.  394).  In  cases  where  the  pelvis  and  ureter  are  single,  the  fusion  may 
have  occurred  secondarily,  although  there  is  the  possibility  that  only  a  single 
anlage  appeared. 

Occasionally  in  children  and  even  in  adults  the  kidneys  show  a  distinct 
tabulation.  This  is  due  to  the  persistence  of  the  lobulation  that  normally 
exists  in  the  foetus  (p.  401). 

The  kidney  may  be  more  or  less  movable  owing  to  laxity  of  the  surrounding 
tissue,  or  it  may  Refloating,  in  which  case  it  has  a  distinct  mesentery.  These 
cases  should  be  distinguished  from  those  in  which  similar  conditions  have  been 
acquired,  usually  as  the  result  of  trauma. 

Congenital  cysts  of  the  kidney  are  not  uncommon.  They  vary  in  size  and 
number,  sometimes  being  so  numerous  that  they  crowd  out  the  greater  part 
of  the  renal  tissue.  Rarely  they  are  so  large  and  numerous  that  the  affected 
organ  fills  a  large  part  of  the  abdominal  cavity,  resulting  in  serious  or  even 
fatal  disturbances  of  the  functions  of  other  organs.  There  are  three  views  con- 
cerning the  origin  of  these  cysts,  (i)  They  may  be  the  result  of  dilatation  of 
certain  renal  tubules  derived  from  the  nephrogenic  tissue,  which  failed  to  unite 
writh  the  straight  tubules  (p.  396).  (2)  Inflammation  in  the  medulla  of  the 
fcetal  kidney  may  effect  a  closure  of  the  lumina  of  some  of  the  tubules,  with 
subsequent  dilatation  of  the  portions  (tubules  or  renal  corpuscles)  that  are  cut 
off  from  communication  with  the  renal  pelvis.  (3)  Normally  some  of  the  renal 
corpuscles  and  tubules  degenerate  (p.  402) ,  and  the  cysts  may  arise  as  dilatations 
of  incompletely  degenerated  corpuscles  or  tubules  or  both.  While  these  views 
appear  reasonable,  none  of  them  has  been  proven.  All  three  views  express 
possibilities,  and  there  is  no  good  reason  for  believing  that  any  one  of  them 
expresses  the  only  possibility. 

THE  URETERS. — The  renal  pelvis  is  sometimes  absent,  the  calyces  uniting 
to  form  two  or  more  tubes  which  in  turn  unite  to  form  the  ureter.  This  prob- 
ably is  the  result  of  abnormal  branching  of  the  ureter  during  development  and 
the  failure  of  the  ends  of  the  branches  to  become  dilated.  Occasionally  the 
ureter  is  double  or  triple  throughout  the  whole  or  a  part  of  its  length.  The 
most  reasonable  explanation  of  two  or  three  complete  ureters  on  either  side  is 
that  two  or  three  separate  evaginations  arose  from  the  mesonephric  duct  (p. 
394.)  Where  the  tube  is  double  in  only  a  part  of  its  length,  an  abnormal 
branching  of  the  single  original  evagination  is  indicated. 

Atresia  of  one  or  both  ureters  is  occasionally  met  with.     This  probably 


THE   DEVELOPMENT   OF  THE   UROGENITAL  SYSTEM.  435 

represents  a  secondary  constriction  after  the  ureter  is  formed  since  both  evag- 
inations  are  hollow  from  the  beginning  (p.  394),  but  the  cause  of  the  constric- 
tion is  not  understood.  The  atresia  results  in  dilatation  of  the  portion  of  the 
ureter  on  the  side  toward  the  kidney. 

Abnormal  situations  of  the  openings  are  sometimes  seen,  the  explanation 
of  which  is  to  be  found  in  the  relations  of  these  tubes  to  the  mesonephric  ducts, 
to  the  cloaca,  and  to  the  Miillerian  ducts.  In  the  male  the  ureters  may  open  into 
the  seminal  vesicles,  the  prostatic  urethra,  or  the  rectum.  If  one  recalls  that 
the  ureter  arises  as  an  evagination  from  the  mesonephric  duct  near  the  opening 
of  the  latter  into  the  cloaca  (p.  394),  that  the  cloaca  becomes  separated  into  a 
dorsal  part  (the  rectum)  and  a  ventral  part  (the  urogenital  sinus)  (p.  403) ,  and 
that  the  proximal  end  of  the  mesonephric  duct  is  so  far  taken  up  into  the  wall 
of  the  urogenital  sinus  (or  bladder)  that  the  ureter  opens  separately  (p.  403),  it  is 
readily  seen  that  any  interference  with  these  normal  processes  of  development 
will  result  in  abnormal  opening  of  the  ureter.  If  the  ureter  does  not  become 
separated  from  the  mesonephric  duct,  it  will  open  into  the  deferent  duct  (vas 
deferens),  the  latter  being  the  proximal  part  of  the  mesonephric  duct.  And 
since  the  seminal  vesicle  is  an  outgrowth  from  the  proximal  end  of  the  meso- 
nephric duct,  the  opening  of  the  ureter  is  likely  to  be  associated  with  the  vesicle. 
If  the  separation  between  the  ureter  and  mesonephric  duct  is  complete,  but 
the  opening  of  the  ureter  does  not  migrate  cranially  on  the  wall  of  the  bladder, 
the  opening  comes  to  lie  in  the  wall  of  the  prostatic  urethra.  If  the  wall 
(urorectal  fold)  separating  the  urogenital  sinus  and  rectum  is  situated  too  far 
dorsally,  the  opening  of  the  ureter  comes  to  be  in  the  wall  of  the  rectum.  (Con- 
sult Figs.  360,  361,  362,  363.) 

In  the  female  the  ureters  may  open  into  the  urethra,  the  vagina,  or  the  uterus. 
The  explanation  of  the  opening  into  the  urethra  is  the  same  as  in  the  male 
(see  preceding  paragraph).  The  opening  into  the  genital  tract  is  probably  to 
be  explained  on  the  ground  that  the  ureters  fail  to  migrate  cranially  along 
the  wall  of  the  urogenital  sinus  to  the  bladder,  and  as  the  fused  ends  of  the 
Miillerian  ducts  enlarge  to  form  the  uterus  and  vagina,  the  openings  of  the 
ureters  are  taken  up  into  their  walls. 

THE  BLADDER. — Absence  of  the  bladder  is  very  rare.  Abnormal  small- 
ness,  due  to  imperfect  dilatation  of  the  urogenital  sinus  (p.  404),  is  not  infre- 
quent. 

The  urachus,  which  represents  the  portion  of  the  allantoic  duct  between 
the  bladder  and  the  umbilicus  (p.  404) ,  not  infrequently  persists  as  a  whole  or 
in  part,  giving  rise  to  certain  anomalous  conditions  in  the  region  of  the  middle 
umbilical  ligament.  The  urachus  may  persist  as  a  complete  tube,  lined 
with  epithelium,  thus  forming  a  means  by  which  urine  can  escape  at  the 
umbilicus.  This  condition  is  usually  associated  with  obstruction  of  the 


436  TEXT-BOOK  OF  EMBRYOLOGY. 

urethra  and  is  known  as  uracho-vesical  fistula.  The  urachus  may  degenerate 
in  part,  leaving  disconnected  portions  which  frequently  become  dilated  to 
form  cysts. 

Vesical  fissure,  the  most  serious  malformation  of  the  bladder,  is  associated 
with  fissure  of  the  lower  abdominal  wall.  The  edges  of  the  cleft  in  the  bladder 
are  continuous  with  those  of  the  cleft  in  abdominal  wall,  the  integument  being 
continuous  with  the  lining  of  the  bladder.  In  some  cases  the  bladder  is 
everted  through  the  cleft,  and  the  cleft  may  even  be  so  extensive  as  to  involve 
the  external  and  internal  genital  organs.  Vesical  fissure  is  much  more  com- 
mon in  the  male  than  in  the  female.  No  very  satisfactory  explanation  of  this 
malformation  has  yet  been  given.  It  is  in  some  way  connected  writh  imperfect 
formation  of  the  ventral  abdominal  wall  resulting  from  influences  acting  at  a 
very  early  period  of  development. 

THE  URETHRA  in  both  sexes  may  be  abnormally  small  or  abnormally  large 
or  partly  occluded,  owing  to  faulty  development  of  the  urogenital  sinus.  In 
the  male  the  penile  portion  also  may  be  malformed,  being  represented  merely 
by  a  furrow  on  the  lower  side  of  the  penis.  This  condition,  known  as  hypo- 
spadias,  is  due  to  the  incomplete  fusion  or  lack  of  fusion  between  the  genital  folds 
along  the  lower  side  of  the  genital  tubercle  (p.  428).  In  extreme  cases  the  de- 
fect may  involve  the  scrotum  and  extend  back  as  far  as  the  prostate  gland,  the 
two  halves  of  the  scrotum  being  separated.  Epispadias,  in  which  the  urethral 
cleft  extends  along  the  upper  side  of  the  penis  (or  the  clitoris)  is  rare,  and  is 
usually  associated  with  vesico-abdominal  fissure.  Its  mode  of  origin  is  not 
understood. 

THE  TESTICLES. — One  of  the  most  common  malformations  affecting  the 
male  genital  glands  is  the  condition  known  as  chryptorchism,  in  which  the 
glands,  instead  of  descending  into  the  scrotum,  are  retained  within  the  ab- 
dominal cavity.  One  or  both  testicles  may  be  affected.  They  may  occupy 
their  original  position  far  forward  in  the  abdominal  cavity  or  may  be  situated 
near  the  inguinal  canal,  or  may  lie  at  some  intermediate  point.  The  malposi- 
tion is  due  to  a  failure  in  the  normal  descent  into  the  scrotum  (p.  423).  The 
cause  of  the  failure  is  obscure.  Not  infrequently  the  ectopic  testicles  atrophy 
or  fail  to  develop  properly  at  puberty. 

Congenital  absence  of  one  or  both  testicles  is  rare.  More  frequently  the 
gland  or  efferent  system  of  ducts  is  defective  in  part,  owing  to  imperfect 
development.  In  case  of  absence  of  the  testicles  the  individual  is  small  and 
poorly  developed ;  when  the  glands  are  imperfectly  developed  the  individual  is 
effeminate. 

Cysts  which  are  sometimes  met  with  in  the  epididymis  are  possibly  due  to 
dilatation  of  incompletely  degenerated  portions  of  the  mesonephric  tubules 
or  Miillerian  ducts.  Teratoid  tumors  and  chorio-epitheliomata  are  occasionally 


THE   DEVELOPMENT   OF  THE   UROGENITAL  SYSTEM.  437 

found  in  the  testicle.  For  a  further  discussion  of  these  see  chapter  on  Terato- 
genesis  (XIX). 

THE  OVARIES. — Congenital  absence  of  both  ovaries  is  rare;  defective 
development  of  one  is  more  common.  Either  anomaly  may  occur  with  or 
without  defects  in  the  other  genital  organs.  Occasionally  the  ovaries  remain 
rudimentary,  their  function  as  egg-producing  organs  never  being  assumed. 
Malpositions,  due  to  partial  or  complete  failure  in  the  normal  descent  into 
the  pelvis  (p.  426),  are  not  infrequent.  Sometimes,  on  the  other  hand,  they 
descend  to  the  inguinal  canal  and  may  even  pass  through  the  latter  into  the 
labia  majora. 

Ovarian  cysts  occur  frequently.  Some  of  these  (follicular  cysts)  may  arise 
during  postnatal  life  as  dilatations  of  Graafian  follicles.  Others  probably 
arise  during  fcetal  life  in  the  same  manner.  Certain  other  forms  of  ovarian 
tumors,  known  as  cystadenomata,  are  possibly  to  be  considered  as  derivatives 
of  the  epithelium  of  the  medullary  cords  which  in  normal  cases  disappear 
entirely  (p.  410;  also  Fig.  366).  A  discussion  of  the  origin  of  teratoid  tumors  of 
the  ovary  will  be  found  in  the  chapter  on  Teratogenesis  (XIX). 

THE  OVIDUCTS,  UTERUS  AND  VAGINA. — Absence  of  the  oviducts  is  usually 
associated  with  malformations  of  other  parts  of  the  genital  tract.  On  the  other 
hand,  normal  oviducts  may  be  present  in  conjunction  with  defective  uterus 
and  vagina.  Atresia  may  occur  at  the  uterine  or  fimbriated  end,  or  at  any 
intermediate  point. 

The  majority  of  the  malformations  of  the -uterus  and  vagina  can  be  at- 
tributed to  defective  processes  of  development  in  the  caudal  ends  of  the  Miiller- 
ian  ducts.  It  will  be  remembered  that  the  caudal  ends  of  these  ducts  normally 
fuse  to  form  a  single  medial  tube  which  opens  into  the  urogenital  sinus,  and 
which  constitutes  the  anlage  of  the  uterus  and  vagina  (p.  419;  Fig.  363).  It  is 
obvious  that  any  defect  in  this  fusion  will  result  in  some  degree  of  duplicity 
in  the  two  organs  in  question.  The  fusion  may  be  almost  complete,  the  result- 
ing abnormality  being  merely  a  small  pocket  which  forms,  at  each  side  of  the 
fundus,  a  continuation  of  the  cavity  of  the  uterus.  There  may  be  a  greater 
degree  of  imperfection  in  the  fusion,  resulting  in  a  partial  division  of  the  uterus 
into  two  horns — bicornuate  uterus.  The  wall  between  the  two  Mullerian  ducts 
may  remain  patent  in  the  entire  uterine  portion  of  the  tract,  thus  giving  rise 
to  a  bipartite  uterus.  If  the  wall  .between  the  ducts  remains  intact  throughout 
both  uterine  and  vaginal  portions,  the  result  is  a  complete  division  of  the  utero- 
vaginal  tract — uterus  didelphys.  Occasionally  the  uterine  portion  of  one 
Mullerian  duct  may  fail  to  develop  properly  and  becomes  a  solid  cord,  resulting 
in  an  unicornuate  uterus. 

Not  infrequently  the  uterus  remains  rudimentary — infantile  uterus.  This 
anomaly  is  usually  accompanied  by  stenosis  of  the  vagina.  Stenosis  or  other 


438  TEXT-BOOK  OF  EMBRYOLOGY. 

defects  in  the  vagina  may  occur,  however,  when  the  uterus  is  normal.  In  rare 
instances  the  hymen  is  absent;  in  other  cases  it  closes  the  entrance  to  the  vagina 
• — a  condition  known  as  imperforate  hymen. 

Malformations  of  the  uterus  and  vagina  resulting  from  persistence  of  the 
cloaca  and  atresia  of  the  anus  are  mentioned  on  page  358. 

HERMAPHRODITISM. 

This  condition  implies  a  combination  of  the  male  and  female  sexual  organs 
in  one  individual,  accompanied  by  a  blending  oi  the  general  characteristics  of 
the  two  sexes  When  such  an  individual  possesses  both  ovary  and  testicle,  the 
condition  is  known  as  true  hermaphroditism;  when  the  individual  possesses 
ovaries  or  testicles,  the  condition  is  known  as  false  hermaphroditism. 

TRUE  HERMAPHRODITISM. — The  presence  of  both  ovary  and  testicle  in  one 
individual  is  one  of  the  rarest  anomalies  in  man.  Furthermore,  one  or  both  of 
the  organs  are  sexually  immature.  Three  forms  can  be  recognized  (Klebs) : 

1 .  Lateral  hermaphroditism,  in  which  an  ovary  is  present  on  one  side  and  a 
testicle  on  the  other; 

2.  Unilateral  hermaphroditism,  in  which  both  ovary  and  testicle  are  present 
on  one  side,  either  ovary  or  testicle,  or  neither,  on  the  other  side; 

3.  Bilateral  hermaphroditism,  in  which  both  ovary  and  testicle  are  present  on 
both  sides. 

In  all  these  cases  the  general  character  of  the  body  is  of  an  intermediate 
type,  sometimes  tending  toward  the  male,  sometimes  toward  the  female.  The 
external  genitalia  are  also  of  an  intermediate  type,  with  hypospadias,  small 
penis,  separate  scrotal  halves,  and  small  vaginal  orifice.  The  uterus  usually 
shows  some  degree  of  duplicity. 

FALSE  HERMAPHRODITISM. — In  this  type  of  hermaphroditism,  in  which 
either  ovaries  or  testicles  are  present  in  an  individual  with  mixed  general 
sexual  characteristics,  two  varieties  can  be  recognized : 

1.  Masculine  false  hermaphroditism,  the  more  common,  in  which  testicles  are 
present  but  the  external  genitalia  and  general  character  of  the  body  approximate 
the  female; 

2.  Feminine  false  hermaphroditism,  in  which  ovaries  are  present  but  other- 
wise male  characteristics  predominate. 

The  causes  underlying  the  origin  of  hermaphroditism  are  among  the  most 
obscure  in  teratogenesis.  It  is  well  known  that  up  to  the  fourth  or  fifth  week 
the  anlagen  of  the  sexual  glands  are  histologically  "indifferent,"  and  later  be- 
come differentiated  into  ovaries  or  testicles  (p.  408).  Since  the  secondary 
sexual  characteristics  are  dependent  upon  the  development  of  the  primary,  they 
also  are  brought  out  later.  If  the  "indifferent"  glands  give  rise  to  both  ovaries 


THE   DEVELOPMENT   OF  THE   UROGENITAL  SYSTEM.  439 

and  testicles,  true  hermaphroditism  is  the  result;  if  they  give  rise  to  either 
ovaries  or  testicles  but  the  external  genitalia  and  general  characteristics  develop 
in  the  opposite  direction,  false  hermaphroditism  is  the  result.  Thus  the  her- 
maphroditic condition  is  potentially  present  in  every  individual  during  the 
earlier  stages  of  development;  the  most  remarkable  fact  is  that  it  is  not  more 
common. 

Recent  researches  in  cytology  have  added  a  new  phase  to  the  question  of  the 
origin  of  hermaphroditism.  Accessory  chromosomes  have  been  demonstrated 
in  the  ova  and  spermatozoa  of  many  species  of  insects  (McClung,  Wilson, 
Morgan)  and  in  ova  and  pollen  of  dioecious  plants  (Correns).  It  has  been 
suggested  that  these  have  some  significance  in  the  determination  of  sex,  the 
female  elements  containing  the  additional  chromatin  elements  (see  p.  416). 
Carrying  this  a  step  further,  Adami  has  suggested  that  "hermaphroditism  is 
based  upon  aberration  in  the  distribution  of  the  chromosomes  in  either  the  ovum 
or  the  spermatozoon." 

PRACTICAL  SUGGESTIONS. 

The  Pronephros. — Being  a  very  rudimentary  structure  in  the  higher  Vertebrates  (especially 
in  Mammals),  the  pronephros  can  be  studied  to  the  best  advantage  in  embryos  of  some  of 
the  lower  forms,  such  as  the  frog.  The  embryos  can  readily  be  obtained  in  the  spring  in 
ponds;  or  perhaps  a  better  method  is  to  collect  the  eggs  during  the  early  cleavages  (which  can 
be  seen  with  the  naked  eye  or  with  the  aid  of  a  hand  lens)  and  allow  them  to  develop  in 
water  in  the  laboratory,  selecting  successive  stages  for  preservation.  Beginning  when  the 
embryos  are  three  to  four  mm.  long,  remove  the  gelatinuous  capsules  and  fix  in  Flemming's 
fluid.  Successive  stages  up  to  any  length  desired  (twelve  to  fifteen  mm.)  should  be  prepared 
in  the  same  manner.  Cut  transverse  serial  sections  in  paraffin  and  stain  with  Heidenhain's 
haematoxylin.  The  embryos  of  four  to  five  mm.  will  show  the  early  stages,  longer  ones,  of 
course,  the  later  stages,  those  of  about  12  mm.  being  especially  good.  The  developing 
pronephroi  are  found  in  the  mesoderm  lateral  to  the  primitive  segments.  The  ducts,  in 
the  same  relative  position,  can  be  traced  through  the  series  of  sections  to  the  tail  region 
where  they  then  bend  ventrally  and  medially  to  open  into  the  gut.  For  technic,  see  Appendix. 

The  Mesonephros. — Chick  embryos  at  the  end  of  the  second  and  during  the  third  and 
fourth  days  of  incubation  are  most  convenient  for  the  study  of  the  early  development  of  the 
mesonephros.  Remove  the  embryo  from  the  egg,  fix  in  Zenker's  fluid,  cut  transverse  serial 
sections  in  paraffin  and  stain  with  Weigert's  haematoxylin  and  eosin.  Time  can  be  saved  by 
staining  in  Mo  with  borax-carmin,  but  the  differentiation  is  less  complete.  The  mesonephroi 
appear  in  the  intermediate  cell  mass  at  about  the  level  of  the  heart,  development  thence 
progressing  caudally.  The  mesonephric  ducts,  which  are  identical  with  the  pronephric 
ducts,  can  be  traced  caudally  until  they  turn  ventrally  and  medially  and  open  into  the  caudal 
end  of  the  gut. 

In  these  embryos  the  formation  of  the  glomeruli  can  be  studied,  likewise  the  increasing 
intimacy  between  the  posterior  cardinal  and  subcardinal  veins  and  the  mesonephric  tubules. 
By  examining  series  of  sections,  the  segmental  mesonephric  branches  of  the  aorta  can  be 
seen. 

The  mesonephroi  at  the  height  of  their  development  can  be  studied  in  human  embryos 


440  TEXT-BOOK  OF  EMBRYOLOGY. 

of  5  to  6  weeks  (about  20  mm.)  or  in  pig  embryos  of  25  to  35  mm.  Fix  the  pig  embryos, 
for  example,  in  Zenker's  fluid  or  Bouin's  fluid,  cut  transverse  sections  in  paraffin  and  stain 
with  Weigert's  haematoxylin  and  eosin.  Serial  sections  are,  of  course,  necessary  if  one 
wishes  to  trace  the  various  structures  or  to  make  reconstructions.  The  mesonephroi  at  this 
stage  extend  from  the  level  of  the  stomach  to  the  pelvic  region  and  fill  a  considerable  portion 
of  the  abdominal  cavity.  The  mesonephric  duct  lies  in  the  peripheral  part  of  the  organ, 
forming  a  rather  wide  tubule;  the  Miillerian  duct  lies  near  by,  forming  a  much  smaller 
tubule;  the  two  ducts  in  the  later  stages  are  embedded  in  an  elevation  on  the  surface  of  the 
organ.  On  the  medial  side  of  the  mesonephros  a  distinct  projection  constitutes  the  genital 
gland. 

The  Kidney. — Fix  a  pig  embryo  of  about  17  mm.  in  Zenker's  fluid  or  Bouin's  fluid. 
Unless  the  embryo  is  to  be  used  for  the  study  of  other  structures  in  the  anterior  region, 
remove  the  anterior  half.  Cut  transverse  serial  sections  of  the  posterior  half  in  paraffin 
and  stain  with  Weigert's  haematoxylin  and  eosin.  The  anlagen  of  the  kidneys  are  found 
at  the  level  of  the  caudal  ends  of  the  mesonephroi.  They  are  situated  lateral  to  the  aorta 
and  are  composed  of  irregular  tubules  surrounded  by  dense  mesenchymal  tissue.  The 
tubules  represent  the  straight  renal  tubules  which  have  grown  out  from  the  renal  pelvis; 
the  latter  is  usually  a  large,  more  centrally  located  space.  The  dense  mesenchymal  tissue  is 
the  nephrogenic  tissue  (metanephric  blastema)  which  gives  rise  to  the  convoluted  renal 
tubules. 

By  following  the  series  of  sections  caudally,  the  renal  pelvis  can  be  traced  to  the  ureter 
and  the  latter  to  its  opening  into  the  mesonephric  duct. 

Further  development  of  the  kidney  can  be  studied  in  sections  of  older  embryos,  prepared 
by  the  same  technic  as  those  used  for  the  earlier  stages  (see  above).  In  more  advanced 
stages  the  anlagen  of  the  convoluted  renal  tubules  are  seen  as  very  dense  portions  of  the 
mesenchymal  tissue,  lying  in  contact  with  the  straight  tubules.  The  cells  become  epithelial 
in  character  and  join  those  of  the  straight  tubules. 

Wax  reconstructions  are  valuable  adjuncts  in  the  study  of  the  kidney.  One  should  be 
made  of  a  kidney  and  ureter  at  an  early  stage  (pig  embryo  of  17  mm.)  and  another  of  a 
group  of  renal  tubules  at  some  later  stage. 

The  Bladder,  etc. — It  is  very  difficult,  by  studying  sections  alone,  to  get  a  comprehensive 
view  of  the  changes  that  occur  in  the  bladder,  in  the  proximal  ends  of  the  ureters  and  meso- 
nephric ducts,  and  in  the  urethra.  Some  idea  of  the  interrelation  of  these  structures  may  be 
gained  by  tracing,  in  serial  sections  of  a  17  mm.  pig  embryo,  the  ureter  to  the  mesonephric 
duct,  the  latter  to  the  urogenital  sinus,  and  the  urogenital  sinus  in  one  direction  to  the  exterior 
and  in  the  other  direction  to  the  urachus.  Prepare  sections  as  under  "The  Kidney"  (see 
above).  At  the  same  time  the  openings  of  the  Miillerian  ducts  on  the  dorsal  side  of  the  uro- 
genital sinus  should  be  noted,  and  the  ducts  traced  forward  through  the  genital  cord,  in 
company  with  the  mesonephric  ducts,  and  along  the  surface  of  the  mesonephroi.  A  wax 
reconstruction  of  all  these  parts  is  very  instructive. 

In  larger  embryos,  the  various  structures  can  be  identified  by  very  careful  dissection. 
Dissections  of  human  embryos  of  two  months  or  more  are  especially  valuable. 

The  Genital  Ridge. — A  single  stage  in  the  development  of  the  genital  ridge  serves  to 
indicate  its  origin  from  the  mesothelium  and  its  primary  location.  Fix  a  pig  embryo  of  10 
to  12  mm.  in  Flemming's  fluid,  making  an  incision  in  the  abdominal  wall  to  give  the  fixa- 
tive access  to  the  interior.  Cut  transverse  sections  in  paraffin  through  the  embryo  at  the 
level  of  the  lower  part  of  the  liver,  and  stain  with  Heidenhain's  haematoxylin.  The  genital 
ridge  is  found  on  the  medial  side  of  the  mesonephros  and  is  composed  of  small,  dark  cells 
and  larger,  clearer  sex  cells, 


THE   DEVELOPMENT   OF  THE  UROGENITAL  SYSTEM.  441 

The  Ovary. — If  the  individual  is  to  be  a  female,  specific  changes  occur  in  the  genital 
ridge  which  lead  to  the  formation  of  the  ovary  (see  page  408  in  text).  The  beginning  of  these 
changes  can  be  seen  in  pig  embryos  of  25  to  30  mm.  (or  human  embryos  of  about  25  mm.), 
prepared  according  to  the  technic  given  under  "The  Genital  Ridge"  (see  p.  440).  The 
ovary  forms  a  fairly  large  ridge  attached  to  the  medial  side  of  the  mesonephros  by  the  meso- 
varium,  but  is  relatively  shorter  than  the  original  genital  ridge.  Cords  of  epithelial  cells 
(the  sex  cords)  extend  into  the  underlying  mesenchymal  tissue  and  are  composed  of  small, 
dark  cells  and  larger,  clearer  cells  (the  primitive  ova,  sex  cells).  It  should  be  borne  in  mind 
that  these  cords  of  cells  are  not  Pfluger's  egg  cords  (which  are  formed  later),  but  that  the 
ones  in  the  anterior  end  of  the  ovary  are  the  forerunners  of  the  rete  cords,  the  ones  in  the 
middle  region  the  forerunners  of  the  medullary  cords. 

For  the  study  of  the  formation  of  Pfluger's  egg  cords,  egg  nests  and  primary  Graafian 
follicles,  remove  the  ovary  from  a  human  foetus  of  seven  to  eight  months,  or  from  any  mam- 
malian embryo  at  a  corresponding  stage  of  development,  fix  in  Flemming's  fluid,  cut  thin 
sections  in  celloidin  and  stain  with  Heidenhain's  haematoxylin. 

For  the  study  of  the  later  development  of  the  Graafian  follicles,  fix  the  ovary  of  an  adult 
cat  or  dog  in  Orth's  fluid,  cut  celloidin  sections  through  the  entire  organ  and  stain  with 
Weigert's  haematoxylin  and  eosin.  These  sections  are  usually  satisfactory  for  the  study  of 
corpora  lutea. 

The  Testicle. — The  beginning  of  the  changes  that  differentiate  the  testicle  from  the 
ovary  can  be  studied  in  sections  of  male  pig  embryos  of  25  to  30  mm.,  prepared  according  to 
the  technic  given  under  "The  Genital  Ridge."  As  in  the  ovary  (see  above),  trabeculae 
of  epithelial  cells  extending  into  the  underlying  mesenchymal  tissue  constitute  the  sex  cords, 
but  the  sex  cells  (forerunners  of  the  spermatogonia)  are  less  clear  and  resemble  the  undiffer- 
entiated  epithelial  cells.  The  sex  cords  in  the  anterior  end  of  the  testicle  are  the  forerunners 
of  the  rete  testis  (which  unites  with  the  mesonephric  tubules)  and  the  straight  tubules;  those 
in  the  middle  region  are  the  forerunners  of  the  convoluted  seminiferous  tubules. 

Sections  of  a  testicle  at  a  later  period  (at  birth,  for  example)  are  very  instructive.  Fix 
the  gland  in  Orth's  fluid,  cut  longitudinal  sections  of  the  entire  organ  through  the  rete  testis, 
including  also  the  epididymis,  and  stain  with  Weigert's  haematoxylin  and  eosin. 

The  descent  of  the  ovaries  and  testicles  can  be  demonstrated  in  dissections  of  human  em- 
bryos of  three  months  and  more.  If  the  dissections  are  carefully  made,  the  bladder  and 
urachus,  the  urogenital  sinus,  and  the  various  ligaments  can  be  identified. 

References  for  Further  Study. 

ADAMI,  J..G.:  The  Principles  of  Pathology.     Vol.  I,  1908. 

AICHEL,  O.:  Vergleichende  Entwickelungsgeschichte  und  Stammesgeschichte  der 
Nebennieren.  Arch.  f.  mik.  Anat..  Bd.  LVL,  1900. 

ALLEN,  B.  M.:  The  Embryonic  Development  of  the  Ovary  and  Testis  in  Mammals. 
Am.  Jour,  of  Anat.,  Vol.  Ill,  1904. 

BEARD,  J.:     The  Germ-cells  of  Prisciurus.     Anat.  Anz.,  Bd.  XXI,  1902. 

BEARD,  J.:  The  Morphological  Continuity  of  the  Germ  Cells  in  Raja  batis.  Anat.  Anz., 
Bd.  XVIII,  1900. 

BONNET,  R.:  Lehrbuch  der  Entwickelungsgeschichte.     Berlin,  1907. 

EIGENMANN,  C.  H.:  On  the  Precocious  Segregation  of  the  Sex-cells  of  Micrometrus 
aggregatus.  Jour  0}  Morphol.,  Vol.  V,  1891. 

FELIX,  W.:  Entwickelungsgeschichte  des  Excretions-systems.  Ergebnisse  der  Anat. 
u.  Entwick.,  Bd.  XIII,  1903. 


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FELIX,  W.,  and  BUHLER,  A.:  Die  Entwickelung  der  Harn-  und  Geschlechtsorgane.  In 
Hertwig's  Handbuch  d.  vergleich.  u.  experiment.  Entwickelungslehre  der  Wirbeltiere,  Bd.  III. 
Teil  I,  1904. 

GAGE,  S.  P. :  A  Three  Weeks'  Human  Embryo,  with  Especial  Reference  to  the  Brain  and 
Nephric  System.  Am.  Jour,  of  Anat.,  Vol.  IV,  1905. 

GERHARDT,  U.:  Zur  Entwickelung  der  bleibenden  Nieren.  Arch.  f.  mik.  Anat.,  Bd. 
LVII,  1901 

HERTWIG,  O.:  Lehrbuch  der  Entwickelungsgeschichte  des  Menschen  und  der  Wirbel- 
tiere. Jena,  1906. 

HILL,  E.  C.:  On  the  Gross  Development  and  Vascularization  of  the  Testis.  Am. 
Jour.  of.  Anat.,  Vol.  VI,  1907. 

HUBER,  G.  C.:  On  the  Development  and  Shape  of  the  Uriniferous  Tubules  of  Certain 
of  the  Higher  Mammals.  Am.  Jour,  of  Anat.,  Vol.  IV,  Suppl.,  1905. 

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Arch.f.  Anat.  u.  Physiol.,  Anat.  Abth.,  1896. 

KOHN,  A.:  Das  chromaffine  Gewebe.     Ergebnisse  der  Anat.  u.  Entwick.,  Bd.  XII,  1903, 

KOLLMAN,  J. :  Lehrbuch  der  Entwickelungsgeschichte  des  Menschen.     Jena,  1898. 

KOLLMAN  J.:  Handatlas  der  Entwickelungsgeschichte  des  Menschen.  Jena,  1907, 
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MARCHAND,  F.:  Missbildungen.  In  Eulenburg's  Real-Encyclopadie  der  gesammten 
Heilkunde,  Bd.  XV,  1897. 

McMuRRiCH,  J.  P.:  The  Development  of  the  Human  Body.     Philadelphia,  1907. 

MINOT,  C.  S.:  Laboratory  Text-book  of  Embryology.     Philadelphia,  1903. 

MORGAN,  T.  H.:  The  Cause  of  Gynandromorphism  in  Insects.  Am.  Naturalist,  Vol. 
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NAGEL,  W. :  Ueber  die  Entwickelung  des  Urogenitalsystems  des  Menschen.  Arch.  f. 
Mik.  Anat.,  Bd.  XXXIV,  1889. 

NAGEL,  W.:  Ueber  die  Entwickelung  der  Urethra  und  des  Dammes  beim  Menschen. 
Arch.  f.  mik.  Anat.,  Bd.  XL,  1892. 

NAGEL,  W.:  Ueber  die  Entwickelung  des  Uterus  und  der  Vagina  beim  Menschen.  Arch, 
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PIERSOL,  G.  A.:  Teratology.  In  Wood's  Reference  Handbook  of  the  Medical  Sciences, 
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POLL,  H.:  Die  Entwickelung  der  Nebennierensysteme.  In  Hertwig's  Handbuch  der 
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SCHREINER,  H.  E.:  Ueber  die  Entwickelung  der  Amniotenniere.  Zeitschr.  f.  wissensch. 
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SOULIE,  A.:  Sur  le  mechanisme  de  la  migration  des  testicules.  Comp.  Rend,  de  la  Soc. 
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SOULIE,  A. :  Recherches  sur  le  developpement  des  capsules  surrenales  chez  les  vertebres 
superieurs.  Jour.  de.  I' Anal,  et  de  la  Physiol.,  T.  XXXIX,  1903. 

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Bd.  XXVIII,  1905. 


THE   DEVELOPMENT  OF  THE  UROGENITAL  SYSTEM.  443 

TAUSSIG,  F.  J. :  The  Development  of  the  Hymen.     Am.  Jour,  of  Anal.,  Vol.  VIII,  1908. 

WIESEL,  J.:  Ueber  die  Entwickelung  der  Nebennieren  des  Schweins,  besonders  der 
Marksubstanz.  Anat.  Hefte,  Bd.  XVI,  1900. 

WILSON,  E.  B.:  Studies  on  Chromosomes.  Jour,  of  Exp.  ZodL,  Vol.  II,  1905,  Vol.  Ill, 
1906.  Vol.  VII,  1909. 

WINIWARTER,  H.:  Recherches  sur  Povogenese  et  1'organogenese  de  1'ovaire  des  Mammi- 
feres.  Arch,  de  Biol.,  T.  XVII,  1900. 

WOODS,  F.  W.:  Origin  and  Migration  of  the  Germ-cells  in  Acanthias.  Am.  Jour,  of 
Anat.,  Vol.  I,  No.  3,  1902. 


CHAPTER  XVI. 
THE  DEVELOPMENT  OF  THE  INTEGUMENTARY  SYSTEM. 

The  integument  consists  of  the  skin  and  certain  accessory  structures.  The 
skin  is  composed  of  the  dermis  (or  corium)  and  the  epidermis.  The  accessory 
structures  comprise  the  hairs,  nails,  sudoriferous  glands,  sebaceous  glands,  and 
mammary  glands.  The  epidermis  (or  epithelial  layer)  and  all  the  accessory 
structures  are  derived  from  the  ectoderm;  the  dermis  is  mesodermal  in  its 
origin.  Other  appendages  of  the  skin — such  as  scales,  feathers,  claws,  hoofs, 
and  horns — which  are  found  only  in  the  lower  animals,  are  ectodermal 
derivatives  and  belong  in  the  same  class  as  the  accessory  structures  in  man. 

The  Skin. 

THE  EPIDERMIS. — The  embryonic  ectoderm  consists  primarily  of  a  single 
layer  of  cells  (Fig.  81).  During  the  latter  part  of  the  first  month,  the  single 
layer  gives  rise  to  two  layers,  of  which  the  outer  is  composed  of  irregular  flat 
cells  and  is  known  as  the  epitrichium  or  periderm,  the  inner  or  basal,  of  larger 
cuboidal  cells  which  are  the  progenitors  of  the  epidermal  cells  and  of  the  acces- 
sory structures.  The  epitrichial  cells  later  become  dome-shaped  and  acquire 
a  vesicular  structure,  the  nuclei  becoming  less  distinct.  They  persist  until  the 
middle  of  foetal  life  and  are  then  cast  off  and  mingle  with  the  secretion  of  the 
newly  formed  sebaceous  glands  as  a  constituent  of  the  vernix  caseosa  (see  p.  449) . 
The  epidermal  cells,  constantly  increasing  in  number,  soon  come  to  form  several 
layers  (4  to  6  in  the  sixth  month).  The  innermost  layer  rests  upon  the  base- 
ment membrane  and  is  composed  of  cuboidal  or  columnar  cells  rich  in  cytoplasm ; 
the  outer  layers  consist  of  irregular  cells  with  clearer  contents  and  less  distinct 
nuclei. 

As  development  proceeds,  the  basal  layer  gives  rise  to  several  layers  which 
together  constitute  the  stratum  germinativum.  The  cells  of  the  innermost 
layers  are  constantly  proliferating  and  thus  forming  new  cells  which  are  pushed 
toward  the  surface.  During  the  seventh  month  keratohyalin  granules  appear 
in  two  or  three  layers  which  are  then  known  collectively  as  the  stratum  granu- 
losum.  The  clearer  cells  of  the  superficial  layers  undergo  a  process  of  de- 
generation by  which  their  contents  are  transformed  into  a  horny  substance, 
the  nuclei  becoming  fainter  and  finally  disappearing.  These  modified  or  degen- 
erated cells,  which  are  constantly  being  cast  off  and  replaced  by  others  from 

444 


THE   DEVELOPMENT  OF  THE   INTEGUMENTARY  SYSTEM.  445 

the  deeper  layers,  constitute  the  stratum  corneum  (Fig.  392).  In  the  thick 
epidermis,  on  the  palms  of  the  hands  and  the  soles  of  the  feet,  for  example,  a 
few  layers  of  cells  just  outside  of  the  stratum  granulosum  become  specially 
modified  (keratinized)  to  form  the  stratum  lucidum. 

THE  DERMIS. — In  the  first  month  the  dermis  is  represented  by  closely  ar- 
ranged, spindle-shaped  mesenchymal  (mesodermal)  cells  underlying  the 
epidermis,  and  is  separated  from  the  latter  by  a  delicate  basement  membrane. 
This  mesenchymal  tissue  gives  rise  to  fibrous  connective  tissue  which,  about 
the  third  month,  becomes  differentiated  into  two  layers — the  dermis  proper 
and  the  deeper  subcutaneous  tissue.  The  papillae  develop  as  little  projections 
of  the  dermis  which  grow  into  the  stratum  germinativum  of  the  epidermis. 
In  some  of  these,  many  blood  vessels  appear,  while  in  others  nerve  endings 

Eponychium 
Root  of  nail  Nail 


Sole  plate 


Phalanx  II 


Sweat  glands 

FIG.  391. — Longitudinal  section  through  the  end  of  the  middle  finger  of  a 
5  months  human  fostus.     Bonnet. 


(tactile  corpuscles  of  Meissner)  develop,  thus  giving  rise  to  vascular  and  nerve 
papillae.  Usually  a  considerable  amount  of  fat  develops  in  the  subcutaneous 
tissue.  Some  of  the  mesencnymal  cells  of  the  dermis  are  transformed  into 
smooth  muscle  cells  which  are  found  in  connection  with  the  hairs  (arrectores 
pilorum),  in  the  scrotum  (tunica  dartos),  and  in  the  nipples. 

The  dermis  has  generally  been  considered  as  a  derivative  of  the  cutis  plates 
(p.  167)  which,  with  the  myotomes,  constitute  the  outer  walls  of  the  primitive 
segments,  but  it  is  probable  that  the  outer  walls  of  the  segments  are  trans- 
formed wholly  into  muscle  tissue  (McMurrich). 

The  pigment  in  the  dermis  develops  in  the  form  of  granules  in  the  connect- 
ive tissue  cells;  that  in  the  epidermis  appears  as  granules  in  the  cells  of  the  deeper 
layers  (white  races)  or  of  all  the  layers  (dark  races).  Whether  the  pigment  in 
the  epidermis  arises  independently  or  is  carried  from  the  dermis  by  wandering 
cells  is  not  known. 


446  TEXT-BOOK  OF  EMBRYOLOGY. 

The  Nails. 

The  nails  are  derivatives  of  the  epidermal  layer  of  the  ectoderm,  and  cor- 
respond morphologically  to  the  claws  and  hoofs  of  lower  animals.  The 
epidermis  on  the  end  of  each  finger  and  toe  forms  a  thickening,  known  as  the 
primitive  nail,  which  is  encircled  by  a  faint  groove  (Zander).  This  occurs 
about  the  ninth  week.  Later  the  nail  area  migrates  to  the  dorsal  side  of  the 
digit  and  becomes  somewhat  sunken  below  the  surface  of  the  surrounding 
epithelium  (Fig.  391).  These  observations  have  led  to  the  conclusion  that 
primarily  the  nails  in  man  occupied  positions  on  the  ends  of  the  digits,  cor- 
responding to  the  positions  of  the  claws  in  lower  forms.  Furthermore,  the  fact 
that  the  nails  (or  their  anlagen)  are  at  first  situated  on  the  ends  of  the  digits  and 
subsequently  migrate  dorsally  would  exolain  the  innervation  of  the  nail  region 
by  the  palmar  (and  plantar)  nerves. 

Strat.  corneum  ~\ 

>  Epidermis 
I     Strat.  germinativum  J 


•'»*     «•*»«*»'          £?" Hair  papilla 

•  •  f 


Con.  tis.  follicle 

Hair  germ 

Hair  papilla  Connective  tissue 

follicle 

FIG.  392. — Vertical  section  of  the  skin  of  a  mouse  embryo  of  18  mm.,  showing 
early  hair  germs.     Maurer. 

After  the  dorsal  migration  of  the  nail  area,  the  epithelium  and  dermis  along 
the  proximal  and  lateral  edges  become  still  more  elevated  to  form  the  nail  wall, 
the  furrow  between  the  latter  and  the  nail  being  the  nail  groove.  At  the  distal 
edge  of  the  nail  area,  the  epithelium  becomes  thickened  to  form  the  so-called 
sole  plate,  which  is  probably  homologous  with  the  more  highly  developed  sole 
plate  in  animals  with  hoofs  or  claws.  The  epithelium  of  the  nail  area  increases 
in  thickness,  and,  as  in  the  skin,  becomes  differentiated  into  three  layers 
(Fig.  391).  The  outer  layers  of  cells  become  transformed  into  the  stratum 
corneum.  The  cells  of  the  next  deeper  layers,  which  acquire  keratin  granules 
and  constitute  the  stratum  lucidum,  degenerate  and  give  rise  to  the  nail  sub- 
stance. Thus  the  nail  is  a  modified  portion  of  the  stratum  lucidum.  The 
layers  of  epithelium  beneath  the  nail  form  the  stratum  germinativum,  which, 
with  the  subjacent  dermis-,  is  thrown  into  longitudinal  ridges. 


THE   DEVELOPMENT   OF  THE  INTEGUMENTARY  SYSTEM.  447 

After  its  first  formation,  the  nail  is  covered  by  the  stratum  corneum  and 
the  epitrichium,  the  two  together  forming  the  eponychium.  The  epitrichium 
soon  disappears;  later  the  stratum  corneum  also  disappears  with  the  exception 
of  a  narrow  band  along  the  base  of  the  nail. 

The  formation  of  nail  substance  begins  during  the  third  or  fourth  month  in 
the  proximal  part  of  the  nail  area.  The  nail  grows  from  the  root  and  from  the 
under  surface  in  the  region  marked  by  the  whitish  color  (the  lunula).  New 
keratinized  cells  are  added  from  the  subjacent  stratum  germinativum  and  be- 
come degenerated  to  form  new  nail  substance  which  takes  the  place  of  the  old  as 
the  latter  grows  distally. 

The  Hair. 

The  hairs,  like  the  nails,  are  derivatives  of  the  epidermal  layer  of  the  ecto- 
derm. In  embryos  of  about  three  months,  local  thickenings  of  the  epidermis 
appear  (beginning  in  the  region  of  the  forehead  and  eye-brows)  and  grow 
obliquely  into  the  underlying  dermis  in  the  form  of  solid  buds — the  hair  germs 
(Fig.  393,  I,  II).  As  the  buds  continue  to  elongate  they  become  club-shaped 
and  the  epithelium  at  the  end  of  each  molds  itself  over  a  little  portion  of  the 
dermis  in  which  the  cells  have  become  more  numerous  and  which  is  known  as 
the  hair  papilla  (Fig.  392). 

As  the  epidermal  bud  grows  deeper,  its  central  cells  become  spindle-shaped 
and  undergo  keratinization  to  form  the  beginning  of  the  hair  shaft;  the  peripheral 
layers  constitute  the  anlage  of  the  root  sheath  (Fig.  393,  III,  IV).  The  hair 
shaft  grows  from  its  basal  end,  new  keratinized  cells  being  added  from  the 
epithelium  nearest  the  papilla  as  the  older  cells  are  pushed  toward  the  surface 
of  the  skin.  The  surface  cells  of  the  hair  shaft  become  flattened  to  form  the 
cuticle  of  the  hair  (Fig.  393,  V).  The  hairs  appear  above  the  surface  about  the 
fifth  month.  Of  the  cells  of  the  root  sheath,  those  nearest  the  hair  become 
scale-like  to  form  the  cuticle  of  the  root  sheath;  the  next  few  layers  become 
modified  (keratinized)  to  form  Huxley's  and  Henle's  layers.  Outside  of  these 
is  the  stratum  germinativum,  the  basal  layer  of  which  is  composed  of  columnar 
cells  resting  upon  a  distinct  basement  membrane.  The  stratum  germinativum 
is  continued  over  the  tip  of  the  papilla,  where  its  cells  give  rise  to  new  cells  for 
the  hair  shaft  (Fig.  393,  V). 

The  connective  tissue  around  the  root  sheath  becomes  differentiated  into  an 
inner  highly  vascular  layer,  the  fibers  of  which  run  circularly,  and  an  outer 
layer,  the  fibers  of  which  extend  along  the  sheath.  The  two  layers  together  con- 
stitute the  connective  tissue  follicle. 

The  first  formed  hairs,  which  are  exceedingly  fine  and  silky,  develop  in  vast 
numbers  over  the  surface  of  the  embryonic  body  and  are  known  collectively  as 
the  lanugo.  This  growth  is  lost  (beginning  before  birth  and  continuing  during 
29 


448 


TEXT-BOOK  OF  EMBRYOLOGY. 


the  first  and  second  years  after),  except  over  the  face,  and  is  replaced  by  coarser 
hairs.     These  in  turn  are  constantly  being  shed  during  the  life  of  the  individual 


'   .»    V*      «J    •  ',-  1 

(».*»,'    '•          '     ,  '      *"'*•••  •' 


II 


f    •••?^/       > 
t       » 


HI        t 


' 


FIG.  393. — Five  stages  in  the  development  of  a  human  hair.     Stohr. 

a,  Papilla;  5,  arrector  pili  muscle;  c,  beginning  of  hair  shaft;  d,  point  where  hair  shaft  grows 
through  epidermis;  e,  anlage  of  sebaceous  gland;  /,  hair  germ;  g,  hair  shaft;  h,  Henle's 
layer;  i,  Huxley's  layer;  k,  cuticle  of  root  sheath;  /,  inner  root  sheath;  m,  outer  root  sheath 
in  tangential  section;  n,  outer  root  sheath;  o,  connective  tissue  follicle. 

and  replaced  by  new  ones.     The  new  hairs  probably  in  most  cases  develop  from 
the  old  follicles,  the  cells  over  the  old  papillae  proliferating  and  the  newly 


THE   DEVELOPMENT  OF  THE  INTEGUMENTARY   SYSTEM.  449 

formed  hairs  growing  up  through  the  old  sheaths.  In  some  cases,  however,  new 
follicles  are  formed  directly  from  the  epidermis  and  dermis.  In  some  of  the 
lower  Mammals,  new  hair  germs  appear  as  outgrows  from  the  sheaths  of  old 
follicles,  thus  giving  rise  to  tufts  of  hair.  The  arrectores  pilorum  muscles  arise 
from  the  dermal  (mesenchymal)  cells  and  become  attached  to  the  follicles  below 
the  sebaceous  glands. 

The  Glands  of  the  Skin. 

THE  SEBACEOUS  GLANDS. — These  structures  usually  develop  in  connection 
with  hairs.  From  the  root  sheath  a  solid  bud  of  cells  grows  out  into'the  dermis 
(Fig.  393,  IV)  and  becomes  lobed.  The  central  cells  of  the  mass  undergo  fatty 
degeneration  and  the  products  of  degeneration  pass  to  the  surface  of  the  skin 
through  the  space  between  the  hair  and  its  root  sheath.  The  more  peripheral 
cells  proliferate  and  give  rise  to  new  central  cells  which  in  turn  are  transformed 
into  the  specific  secretion  of  the  gland,  the  whole  process  being  continuous.  On 
the  margins  of  the  lips,  on  the  labia  minora  and  on  the  glans  penis  and  prepuce, 
glands  similar  in  character  to  the  sebaceous  glands  arise  directly  from  the 
epidermis  independently  of  hairs. 

THE  SUDORIFEROUS  GLANDS. — The  sweat  glands  begin  to  develop  during 
the  fifth  month  as  solid  cylindrical  growths  from  the  deeper  layers  of  the  epider- 
mis into  the  dermis  (Fig.  391).  Later  the  deeper  ends  of  the  cylinders  become 
coiled  and  lumina  appear.  The  lumina  do  not  at  first  open  upon  the  surface 
but  gradually  approach  it  as  the  deeper  epidermal  layers  replace  the  more 
superficial. 

THE  VERNIX  CASEOSA. — During  fcetal  life  the  secretion  of  the  sebaceous 
glands  becomes  mingled  with  the  cast-off  epitrichial  and  epidermal  cells  to  form 
the  whitish  oleaginous  substance  (sometimes  called  the  smegma  embryonum) 
that  covers  the  skin  of  the  new-born  child.  It  is  collected  especially  in  the 
axilla,  groin  and  folds  of  the  neck. 

THE  MAMMARY   GLANDS. 

In  embryos  of  six  to  seven  mm.,  or  even  less,  a  thickening  of  the  epidermis 
occurs  in  a  narrow  zone  along  the  ventro-lateral  surface  of  the  body  (Strahl). 
In  embryos  of  1 5  mm.  this  thickening,  known  as  the  milk  ridge,  extends  from  the 
upper  extremity  to  the  inguinal  region  (Kallius,  Schmidt).  Later  the  caudal 
end  of  the  ridge  disappears,  while  the  cephalic  portion  becomes  more  prominent. 
The  further  history  of  the  ridge  has  not  been  traced,  but  in  embryos  considerably 
older  the  anlage  of  each  gland  is  a  circular  thickening  of  the  epidermis  in  the 
thoracic  region,  projecting  into  the  underlying  dermis.  It  seems  most  probable 
that  this  local  thickening  represents  a  portion  of  the  original  ridge,  the  remainder 


450  TEXT-BOOK  OF  EMBRYOLOGY. 

having  disappeared.  Later  the  central  cells  of  the  epidermal  mass  become 
cornified  and  are  cast  off,  leaving  a  depression  in  the  skin  (Fig.  394).  In  em- 
bryos of  250  mm.  a  number  of  solid  secondary  buds  have  grown  out  (Fig.  395). 
These  resemble  the  anlagen  of  the  sweat  glands,  to  which  they  are  generally 
considered  as  closely  allied  (Hertwig,  Wiedersheim  and  others) ,  and  represent 
the  excretory  ducts.  Continued  evaginations  from  the  terminal  parts  of  the 
excretory  ducts  form  the  lobular  ducts  and  acini.  The  acini,  however,  are 
scarcely  demonstrable  in  the  male,  and  not  even  in  the  female  until  pregnancy. 
Lumina  appear  by  a  separation  and  breaking  down  of  the  central  cells  of  the 
ducts  and  acini,  the  peripheral  cells  remaining  as  their  lining. 

Nipple 
Epitrichium  depression  Dermis 


FIG.  394. — Vertical  section  through  the  anlage  of  the  mammary  gland  of 
a  human  foetus  of  16  cm.     Bonnet. 

Late  in  fcetal  life,  or  sometimes  after  birth,  the  original  depressed  gland 
area  becomes  elevated  above  the  surface  to  form  the  nipple.  The  excretory 
ducts  (15  to  20  in  number)  which  at  first  opened  into  the  depression,  thus  come 
to  open  on  the  surface  of  the  nipple.  In  the  area  around  the  nipple — the 
areola — numerous  sudoriferous  and  sebaceous  glands  develop,  some  of  which 
come  to  open  into  the  lacteal  ducts.  Sometimes  rudimentary  hairs  appear. 
Other  glands — known  as  areolar  glands  (of  Montgomery) — resembling  rudi- 
mentary mammary  glands  also  develop  from  the  epidermis  of  the  areola. 

After  birth  the  mammary  glands  continue  to  grow  slowly  in  both  sexes  up  to 
the  time  of  puberty.     After  this  they  cease  to  grow  in  the  male,  and  then  atrophy.  ] 
In  the  female,  growth  of  the  glandular  elements  goes  on,  but  very  slowly,  and  I 
usually  a  considerable  amount  of  fat  develops  in  the  surrounding  tissue,  I 
causing  the  enlargement  of  the  breasts. 

The  Mammary  Glands  of  Pregnancy. — Even  in  the  female,  as  stated  before, , 
acini  are  scarcely  demonstrable  until  pregnancy.  The  mamma  consists 


THE   DEVELOPMENT   OF  THE  INTEGUMENTARY   SYSTEM. 


451 


mostly  of  connective  tissue  and  fat,  with  scattered  groups  of  duct-like  tubules. 
During  pregnancy  the  tubules  give  rise  to  the  acini  by  a  process  of  evagination, 
the  cells  increasing  in  number  by  mitosis.  Toward  the  end  of  pregnancy  each 
excretory  duct  and  its  smaller  ducts  and  acini  form  a  distinct  lobe  with  a  rela- 
tively small  amount  of  connective  tissue.  The  epithelium  is  low  or  cuboidal, 
and  fat  begins  to  accumulate,  in  the  seventh  or  eighth  month,  as  droplets  in  the 
basal  parts  of  the  cells.  The  droplets  increase  in  number  and  in  size,  approach- 
ing the  inner  end  of  the  cell,  until  finally  the  cell  is  practically  filled.  At  the 
beginning  of  lactation  the  fat  escapes  into  the  lumen  of  the  acinus,  leaving  a  bit 
of  ragged  cytoplasm  with  a  nucleus.  This  regenerates  into  a  cell  capable  of 


fc-;.  W 


Stroma 
FIG.  395. — Vertical  section  of  the  anlage  of  the  mammary  gland  of  a  human  foetus  of  25  cm.    Nagel. 


further  activity;  and  it  is  probable  that  the  same  cell  may  become  filled  with 
fat  and  discharge  its  contents  several  times  during  lactation. 

During  pregnancy  and  lactation  the  acini  also  contain  leucocytes  which  have 
wandered  through  the  epithelium  from  the  surrounding  tissue.  These  contain 
fat  droplets  and  are  known  as  colostrum  corpuscles. 

At  the  end  of  lactation  the  acini  atrophy  and  disappear,  the  lobules  becoming 
masses  of  connective  tissue  and  fat,  which  contain  groups  of  duct-like  tubules 
and  which  are  so  closely  joined  with  one  another  that  they  are  indistinguishable 
as  lobules. 

Anomalies. 

ANOMALIES  OF  THE  SKIN. — The  epidermis  may  develop  to  an  abnormal  de- 
gree over  the  entire  surface  of  the  body,  forming  a  horny  layer  which  is  broken 
only  where  the  skin  is  folded  by  the  movement  of  the  members  of  the  body — 
a  condition  known  as  hyperkeratosis.  Or  the  abnormal  development  may  give 
rise  to  irregular  patches  of  thick  epithelium — ichthyosis.  In  either  case,  hairs 
and  sebaceous  glands  arc  usually  absent  over  the  affected  areas. 


452  TEXT-BOOK  OF  EMBRYOLOGY. 

Occasionally  pigment  develops  in  excess  over  larger  or  smaller  areas  of  the 
skin,  giving  rise  to  the  so-called  ncevi  pigmentosi.  In  some  cases,  on  the  other 
hand,  there  is  total  or  almost  total  lack  of  pigment  in  the  skin  and  hair  (usually 
accompanied  by  defective  pigmentation  of  the  iris,  chorioid  and  retina)— 
a  condition  known  as  albinism.  There  are  also  instances  of  partial  albinism. 
The  influence  of  heredity  in  albinism  is  doubtful,  for  albinos  are  usually  the 
children  of  ordinary  parents. 

The  angiomata  (lymphangiomata,  haemangiomata)  found  in  the  skin  are  due 
to  dilated  lymphatic  or  blood  channels,  the  color  in  haemangiomata  being  due 
to  the  haemoglobin  in  the  blood. 

Dermoid  Cysts. — The  congenital  dermoid  cysts  not  infrequently  found  in  or 
under  the  skin  are  usually  situated  in  or  near  the  line  of  fusion  of  embryonic 
structures,  as  in  the  region  of  the  branchial  arches,  along  the  ventral  body 
wall  and  on  the  back.  During  the  fusion  of  adjacent  structures,  portions  of  the 
epidermis  become  constricted  from  the  parent  tissue  and  come  to  lie  in  the  der- 
mis,  where  they  continue  to  grow  and  produce  cystic  masses  and  sometimes 
give  rise  to  hairs  and  sebaceous  glands.  This  type  of  dermoid  is  to  be  dis- 
tinguished from  that  found  for  example  in  the  ovary,  in  which  derivatives  of 
all  three  germ  layers  are  present  (see  Chap.  XIX). 

ANOMALIES  OF  THE  EPIDERMAL  DERIVATIVES. — Occasionally  hair  develops 
in  profusion  over  areas  of  the  skin  that  naturally  possess  only  a  fine,  silky  growth, 
such,  for  example,  as  a  woman's  face.  Or  nearly  the  entire  body  may  be 
covered  by  an  unusual  amount  of  hair.  Such  conditions — known  as  hyper- 
trichosis — possibly  represent  the  persistence  and  continued  growth  of  the 
lanugo  (p.  447)  and  in  this  sense  are  to  be  regarded  as  the  result  of  arrested 
development  (Unna,  Brandt).  Congenital  absence  of  the  hair  (hypotrichosis, 
alopecia)  is  a  rare  anomaly  and  is  usually  accompanied  by  defective  develop- 
ment of  the  teeth  and  nails. 

Sebaceous  cysts,  generally  regarded  as  due  to  accumulation  of  secretion 
in  the  sebaceous  glands,  sometimes  probably  represent  remnants  of  displaced 
pieces  of  epidermis  apart  from  the  hairs  (Chiari) . 

Supernumerary  mammary  glands  (hypermastid)  and  nipples  (hyperthelia)  are 
not  infrequently  present  in  both  males  and  females.  They  are  usually  situated 
below  the  normal  mammae  (rarely  in  the  axillary  region),  in  a  line  drawn  from 
the  axilla  to  the  groin,  and  probably  represent  persistent  and  abnormally  de- 
veloped portions  of  the  milk  ridge  (see  p.  449)  In  very  rare  cases  a  super- 
numerary gland  develops  in  some  other  region  (even  on  the  thigh) .  If  the 
mammary  glands  are  morphologically  allied  to  the  sweat  glands  (p.  450),  these 
misplaced  mammae  are  suggestive  of  anomalous  development  of  some  of  the 
sweat  gland  anlagen. 


THE   DEVELOPMENT  OF  THE  INTEGUMENTARY   SYSTEM.  453 

PRACTICAL  SUGGESTIONS. 

For  study  of  the  early  epidermal  and  epitrichial  layers  and  dermis,  fix  a  pig  embryo  of 
25  to  30  mm.  in  Zenker's  or  Bouin's  fluid,  cut  sections  in  celloidin,  and  stain  with  Weigert's 
haematoxylin  and  eosin  (see  Appendix). 

For  later  stages  of  the  skin  and  the  formation  of  hair  follicles  and  papillae,  cut  pieces 
from  the  skin  and  deeper  tissues  of  a  pig  embryo  of  5  to  6  inches  and  treat  according  to  the 
above  technic,  cutting  sections  at  right  angles  to  the  surface  of  the  skin.  If  the  hair  follicles 
are  far  enough  advanced,  the  anlagen  of  the  sebaceous  glands  can  be  seen  as  buds  on  the 
root  sheaths.  The  eyelids  of  a  human  foetus  of  about  three  months  afford  especially  good 
material  for  the  study  of  sebaceous  glands. 

For  early  stages  of  the  developing  nails,  treat  the  ends  of  the  fingers  and  toes  of  a  human 
foetus  of  three  months  according  to  the  technic  given  above,  cutting  longitudinal  sections  at 
right  angles  to  the  surface  of  the  nails.  For  the  later  stages  (formation  of  nail  substance, 
etc.)  treat  the  ends  of  the  digits  of  an  embryo  of  five  months  as  above.  The  anlagen  of  the 
sweat  glands  can  also  be  seen  as  cylindrical  growths  of  the  epidermis  into  the  dermis. 

The  milk  ridge  shows  very  clearly  in  young  pig  embryos  (20  mm.  or  more).  Transverse 
sections  of  the  ridge,  prepared  according  to  the  technic  given  in  the  first  paragraph,  are  very 
instructive,  as  are  also  sections  of  the  mammary  glands  of  a  new-born  child. 

References  for  Further  Study. 

BROUHA:  Recherches  sur  les  diverses  phases  du  developpement  et  de  Pactivite  de  la 
mammelle.  Arch,  de  Biol.,  T.  XXI,  1905. 

BONNET,  R. :  Die  Mammarorgane  im  Lichte  der  Ontogenie  und  Phylogenie.  Ergebnisse 
d.  Anat.  u.  Entwick.,  Bd.  II,  1892;  Bd.  VII,  1898. 

KALLIUS,  E.:  Ein  Fall  von  Milchleiste  bei  einem  menschlichen  Embryo.  Anat.  Hefte, 
Bd.  VIII,  1897. 

KEIBEL,  F.,  and  MALL,  F.  P.:  Manual  of  Human  Embryology,  Vol.  I,  1910. 

KRAUSE,  W.:  Die  Entwickelung  der  Haut  und  ihrer  Nebenorgane.  In  Hertwig's 
Handbuch  d.  vergleich.  u.  experiment.  Entwickelungslehre  der  Wirbeltiere,  Bd.  II,  Teil  I,  1902. 

OKAMURA,  T.:  Ueber  die  Entwickelung  des  Nagels  beim  Menschen.  Arch.  f.  Der- 
matol.  u.  SyphiloL,  Bd.  XXV,  1900. 

PIERSOL,  G.  A. :  Teratology.  In  Wood's  Reference  Handbook  of  the  Medical  Sciences, 
Vol.  VII,  1904. 

SCHMIDT,  H.:  Ueber  normale  Hyperthelie  menschlicher  Embryonen  und  iiber  die 
erste  Anlage  der  menschlichen  Milchdriisen  viberhaupt.  Morphol.  Arbeiten,  Bd.  XVII,  1897. 

SCHULTZE,  O.:  Ueber  die  erste  Anlage  des  Milchdriisen  Apparates.  Anat.  Anz.,  Bd. 
VIII,  1892. 

STOHR,  P.:  Entwiekelungsgeschichte  des  menschlichen  Wollhaares.  Anat.  Hefte, 
Bd.  XXIII,  1903. 

STRAHL,  H.:  Die  erste  Entwickelung  der  Mammarorgane  beim  Menschen.  Verhandl. 
d.  Anat.  Gesellsch.,  Bd.  XII,  1898. 

ZANDER,  R.:  Bie  friihesten  Stadien  der  Nagelentwickelung  und  ihre  Beziehungen  zu 
den  Digitalnerven.  Arch.  f.  Anat.  u.  Physiol.,  Anat.  Abth.,  1884, 


CHAPTER  XVII. 
THE  NERVOUS  SYSTEM. 

BY  OLIVER  S.   STRONG. 

GENERAL  CONSIDERATIONS. 

There  are  certain  features  of  the  nervous  system  in  general  and  particularly 
of  the  vertebrate  nervous  system,  the  comprehension  of  which  makes  the 
processes  of  development  of  the  nervous  system  in  man  more  intelligible. 
First,  the  nervous  systems  of  the  lower  Vertebrates  are  in  many  respects 
simpler  than  those  of  higher  forms  and  their  variations  throw  light  upon  the 
causes  which  determine  neural  structures.  Second,  as  the  nervous  systems  of 
all  Vertebrates  develop  from  the  same  germ  plasm,  there  are  resemblances 
between  certain  features  of  both  the  embryonic  and  adult  systems  of  lower 
vertebrates  and  certain  developmental  stages  in  the  higher.  Certain  struc- 
tures met  with  in  lower  adult  forms  may  be  regarded  as  representing  stages 
of  arrested  development — although  specialized  and  aberrant  in  many  respects 
— of  structures  found  in  higher  forms.  Vestigial  structures  in  the  developing 
nervous  systems  of  higher  forms  may  be  regarded  as  recurring  developmental 
necessities  in  the  attainment  of  the  adult  form. 

Stated  in  the  most  general  terms,  coordination  of  bodily  activities  in  response 
to  both  external  and  internal  conditions  is  the  biological  significance  of  the 
nervous  system.  This  implies  a  transmission  of  some  form  of  change  from  one 
part  to  another  or,  in  other  words,  conduction.  This  functional  necessity  is 
shown  structurally  in  the  elongated  form  of  the  histological  elements  of  the 
nervous  system.  That  such  changes  habitually  pass  along  each  element  or 
neurone  in  some  one  direction  seems  to  find  a  natural  structural  expression  in 
the  receptive  body  and  dendrites  of  the  neurone,  and  in  its  long  transmitting 
axone. 

It  is  also  evident  that  coordination  can  only  be  performed  by  a  transmission 
of  a  change  from  some  given  structure  either  back  to  that  structure  or  to  some 
other  structure  to  cause  a  responsive  change.  We  thus  have  not  only  in  the 
vertebrate,  but  at  a  very  early  stage  in  the  invertebrate  nervous  system,  a  dif- 
ferentiation into  afferent  and  efferent  components,  the  two  together  usually 
being  termed  the  peripheral  nervous  system.  The  histological  elements  of  these 
components  are  the  afferent  and  efferent  peripheral  neurones.  All  structures 
which  are  so  affected  as  to  transmit  the  change  to  the  afferent  peripheral  neu- 

454 


THE  NERVOUS   SYSTEM. 


455 


rones  may  be  conveniently  termed  receptors,  those  structures  affected  by  the 
efferent  peripheral  neurones  may  be  termed  effectors  (Sherrington).  Receptors 
include  various  "sensory"  structures  whose  principal  function  appears  to  be 
to  limit  to  some  particular  kind  of  stimulus  the  changes  affecting  the  afferent 
nervous  elements  connected  with  them.  Effectors  include  various  structures 
(muscles,  glandular  epithelia)  whose  activities  are  influenced  by  the  nervous 
system  (Fig.  396).  A  primitive  nervous  mechanism,  thus  composed  of  (i) 
afferent  peripheral  neurones  which  transmit  the  stimulus  from  a  receptor  to 
(2)  efferent  peripheral  neurones  which  in  turn  transmit  the  stimulus  to  an 
effector,  is  a  simple,  two-neurone  reflex  arc  (Fig.  396). 

At  the  same  time  these  neurones,  as  they  increase  in  number,  are  obviously 
brought  into  relation  with  each  other  with  more  economy  of  space  by  having 


Receptor 


Effector 


FIG.  396.- — A  two-neurone  reflex  arc  in  a  Vertebrate,     gg.    Ganglion,     van  Cehuchten 


common  meeting  places.  This,  together  with  the  factor  noted  below,  leads  to 
the  concentration  of  an  originally  diffuse  nervous  system,  spread  out  principally 
in  connection  with  the  outer  (ectodermal)  surface,  into  a  more  centralized 
(ganglionic)  type  of  nervous  system,  which  at  the  same  time  has  in  part  re- 
treated from  the  surface  layer  (ectoderm)  from  which  it  was  originally  derived 

(Fig.  397)- 

Furthermore,  when  we  consider  the  great  number  of  receptors  and  effectors 
in  even  simple  forms,  it  is  apparent  that  for  effective  coordination  there  must  be 
a  considerable  degree  of  complexity  of  association  between  the  afferent  and 
efferent  neurones.  These  associations  may  be  to  some  extent  accomplished  by 
various  branches  of  the  afferent  and  efferent  neurones  coming  directly  into 
various  relations  with  each  other,  but  it  is  also  evident  that  when  a  certain 


456 


TEXT-BOOK  OF  EMBRYOLOGY. 


degree  of  complexity  is  reached,  such  an  arrangement  would  necessitate  an 
extraordinary  number  of  afferent  and  efferent  neurones  or  an  extraordinary 
development  of  branches  of  each  where  they  connect.  Accordingly  we  find  a 
second  category  of  neurones,  the  intermediate  or  central  neurones  which  mediate 


Lumbncus 


Nereis 


FIG.  397. — Illustrating  the  withdrawal  from  the  surface  of  the  bodies 
of  the  afferent  peripheral  neurones.     After  Retzius. 

between  the  afferent  and  efferent  peripheral  neurones.  These  central  neurones, 
together  with  portions  of  peripheral  neurones  in  immediate  relation  with  them, 
form,  in  all  fairly  well  differentiated  nervous  systems,  including  those  of  all 
Vertebrates,  the  central  as  distinguished  from  the  peripheral  nervous  system. 


FIG.  398. — A  three-neurone  reflex  arc.     van  Cehuchten. 
I,  Afferent  peripheral  neurone;  2,  intermediate  or  central  neurone;  3,  efferent  peripheral  neurones. 

The  change  or  stimulus  would  now  pass  from  receptor  through  (i)  afferent 
peripheral  neurones,  (2)  intermediate  neurones,  (3)  efferent  peripheral  neu- 
rones to  effector.  This  arrangement  constitutes  a  three-neurone  reflex  arc 


THE  NERVOUS   SYSTEM.  457 

(Fig.  398),  and  is  evidently  capable  of  complicated  combinations  which  may 
be  further  increased  in  complexity  by  the  intercalation  in  the  arc  of  other 
intermediate  neurones.  Finally,  in  the  central  nervous  system  certain  struc- 
tures consisting  of  intermediate  neurones  are  developed  which  represent  the 
mechanisms  for  certain  coordinations  of  the  highest  order.  Such  are  the 
higher  coordinating  centers  (suprasegmental  structures  of  Adolf  Meyer). 

As  a  result  of  the  preceding,  it  follows  that  in  seeking  the  explanation  for 
various  nervous  structures  there  must  always  be  kept  in  mind,  first,  their  correla- 
tion with  peripheral  structures  and,  second,  the  degree  of  development  of  the 
central  coordinating  mechanism  represented  by  the  intermediate  or  central 
neurones.  The  most  important  features  common  to  the  nervous  systems  of 
all  Vertebrates  owe  their  uniformity  either  to  a  corresponding  uniformity  in 
the  peripheral  receptors  and  effectors,  or  to  a  uniformity  in  the  coordinations  of 
the  stimuli  received  and  given  out  by  the  central  nervous  system.  Variations 
in  structure  are  due  to  variations  of  either  the  peripheral  or  central  factor  above 
mentioned.  In  the  lower  Vertebrates  the  former  factor  plays  a  relatively  more 
important  part  than  in  the  higher  Vertebrates,  the  central  apparatus  being 
simpler;  while  in  the  development  of  the  higher  vertebrate  nervous  systems  the 
dominating  factor  is  the  increasing  complexity  of  the  central  mechanism.  The 
superiority  of  the  nervous  system  of  man  does  not  consist,  in  the  main,  of  supe- 
riority in  sense  organs  or  motor  apparatus,  but  in  the  enormous  development  of 
the  intermediate  neurone  system. 

GENERAL  PLAN  OF  THE  VERTEBRATE  NERVOUS  SYSTEM. 

The  Vertebrate  is  an  elongated  bilaterally  symmetrical  animal  progressing 
in  a  definite  direction,  primitively  perhaps  by  alternating  lateral  contractions 
performed  by  a  segmented  lateral  musculature.  Associated  with  these  char- 
acteristics are  the  bilateral  character  of  the  nervous  system  and  its  transverse 
segmentation,  shown  by  its  series  of  nerves,  a  pair  to  each  muscle  segment. 
The  definite  direction  of  progression  involves  a  differentiation  of  the  forward 
extremity  of  the  animal,  such  as  the  location  there  of  the  mouth  and  respiratory 
apparatus  and  the  development  there  of  specialized  sense  organs,  the  nose,  eye, 
ear,  lateral  line  organs,  and  taste  buds,  which  increase  the  range  of  stimuli 
received  by  the  animal  and  thereby  render  possible  a  greater  range  of  responsive 
activities  in  obtaining  food  and  in  reproduction.  As  a  natural  outgrowth 
of  these  specializations,  the  highest  development  of  the  central  coordinating 
mechanism  also  takes  place  at  the  forward  end  or  head.  This  concentration 
and  development  of  various  mechanisms  in  the  anterior  end  is  usually  termed 
cephalization,  and  is  a  tendency  exhibited  also  by  various  groups  of  Inverte- 
brates in  which  the  same  general  conditions  are  present. 

The  typical  vertebrate  nervous  system,  then,  consists  of  a  bilateral  central 


458  TEXT-BOOK  OF  EMBRYOLOGY. 

nervous  system  connected  by  means  of  a  series  of  segmental  nerves  with  per- 
ipheral structures  (receptors  and  effectors)  and  exhibiting  at  its  anterior  ex- 
tremity a  higher  development  and  specialization  in  both  its  peripheral  and 
central  parts. 

The  general  features  of  the  typical  vertebrate  nervous  system  are  best 
revealed  by  a  brief  examination  of  certain  stages  in  its  development. 

The  entire  nervous  system,  except  the  olfactory  epithelium  and  parts  of 
certain  ganglia  (see  p.  459),  is  derived  ontogenetically  from  an  elongated  plate 
of  thickened  ectoderm,  the  neural  plate.  This  plate  extends  longitudinally  in 
the  axis  of  the  developing  embryo,  its  position  being  usually  first  indicated 
externally  by  a  median  groove,  the  neural  groove  (Fig.  410),  the  edges  of  the 
plate  being  elevated  into  the  neural  folds  (Fig.  411).  The  neural  folds  are 
continuous  around  the  cephalic  end  of  the  plate,  but  diverge  at  the  caudal 
end,  enclosing  between  them  in  this  region  the  blastopore.  Even  at  this  stage, 
the  neural  plate  is  usually  broader  at  its  cephalic  end,  thereby  indicating  already 
the  future  differentiation  into  brain  and  spinal  cord  (Fig.  413).  The  neural 
folds  now  become  more  and  more  elevated  (Fig.  412),  presumably  due  in 
part  to  the  growth  of  the  whole  neural  plate,  and  finally  meet  dorsally  and  fuse, 
thus  forming  the  neural  tube  (Figs.  72  and  429).  The  fusion  of  the  lips  of  the 
neural  plate  to  form  the  neural  tube  usually  begins  somewhere  in  the  middle 
region  of  the  plate  and  thence  proceeds  both  forward  and  backward  (Fig.  119). 
The  last  point  to  close  anteriorly  is  usually  considered  as  marking  the  cephalic 
extremity  of  the  neural  tube,  and  is  called  the  anterior  neuropore. 

Even  before  the  neural  plate  closes  to  form  the  tube,  there  is  often  a  differen- 
tiation of  cells  along  each  edge,  forming  an  intermediate  zone  between  the 
neural  plate  and  the  non-neural  ectoderm  (Fig.  429).  As  the  neural  plate 
becomes  folded  dorsally  into  the  neural  tube  these  two  zones  are  naturally 
brought  together  at  the  point  of  fusion  of  the  dorsal  lips  of  the  neural  plate. 
The  two  zones  thus  brought  together  are  not  included  in  the  wall  of  the  neural 
tube,  but  form  a  paired  or  unpaired  ridge  of  cells  lying  along  its  dorsal  surface. 
This  ridge  of  cells  is  called  the  neural  crest  (Fig.  429).  Later,  each  half  of  the 
neural  crest  separates  from  the  other  half  and  from  the  neural  tube  and  passes 
ventrally  down  along  the  sides  of  the  tube,  at  the  same  time  becoming  trans- 
versely divided  into  blocks  of  cells  (Fig.  434).  These  masses  of  cells  are  the 
rudiments  of  the  cerebrospinal  ganglia  and  differentiate  into  the  afferent  per- 
ipheral neurones,  and  into  some  at  least  of  the  efferent  peripheral  visceral  neu- 
rones (sympathetic)  as  well  as  some  other  accessory  structures  (see  pp.  496 
to  501).  The  peripheral  processes  of  these  ganglion  cells  (afferent  peripheral 
nerve  fibers]  pass  to  the  receptors,  the  central  processes  (afferent  root  fibers)  enter 
the  dorsal  part  of  the  nerve  tube  (Fig.  430).  In  the  case  of  the  special  sense 
organs  there  is  an  interesting  tendency  on  the  part  of  portions  of  the  neural 


THE  NERVOUS   SYSTEM. 


459 


tube,  either  evaginations  (optic  vesicles,  olfactory  bulbs),  or  ganglia,  to  fuse 
with  ectodermal  thickenings  (placodes)  at  the  site  of  the  future  sense  organs. 
There  appear  to  be  often  two  series  of  ganglionic  placodes  in  the  head,  a 
dorsal  (suprabranchial)  series  and  a  ventral  (epibranchial)  series,  the  latter 
being  often  known  as  gill  cleft  organs.  The  former  appear  to  be  especially 
connected  with  the  development  of  the  acustico-lateral  system,  the  latter  prob- 
ably with  the  gustatory  (see  p.  469).  (Fig.  399).  The  bodies  of  the  efferent 


Neural  crest  cells  --^Sji^f-f.*  * 

/•     $  -  "•  ••'«     a 

,  -.«i*' 

jj,'" 
Suprabranchial  placode  --^»^ 


«c- 
'^  d-    Notochord 


—  Preoral  gut 


FIG.  399.  —  Transverse  section  through  the  head  of  a  7  day  Ammocoetes  in  the  region 
of  the  trigeminal  ganglion,     -von  Kupfier. 

neurones  (except  the  sympathetic)  remain  in  the  neural  tube,  lying  .  in  its 
ventral  half,  and  send  their  axones  out  as  the  efferent  peripheral  nerve  fibers  to 
the  effectors. 

The  formation  of  the  neural  plate  and  its  closure  into  a  tube  are  the  em- 
bryological  expression  of  the  above  noted  tendency  of  highly  specialized  neural 
structures  to  concentrate  and  withdraw  from  the  surface  (p.  455).  The  same 
is  true  of  the  less  highly  specialized  placodes,  in  which  this  process  is  not  carried 
so  far.  The  neural  plate  may  thus  be  regarded  as  the  oldest  placode.  The 
afferent  peripheral  neurones  would  naturally  originate  from  the  borders  of  this 
plate,  such  portions  being  the  last  to  separate  from  the  non-neural  ectoderm 
or  outer  surface.  They  may  be  regarded  as  the  youngest  portions,  phylo- 
genetically,  of  the  plate,  and  there  seems  to  be  some  variation  among  Chordates 
as  to  the  degree  of  inclusion  of  the  afferent  peripheral  neurones  in  the  plate. 

In  the  neural  tube  thus  formed,  there  can  be  distinguished  four  longitudinal 


460 


TEXT-BOOK  OF  EMBRYOLOGY. 


plates  or  zones :    A  ventral  median  plate  (floor  plate) ,  a  dorsal  median  plate  (roof 
plate),  where  the  fusion  occurred,  and  two  lateral  plates  (e.g.,  Fig.  442). 

Two  points  are  to  be  noted:  First,  that  the  neural  plate  is  a  bilateral  struc- 
ture and  the  future  development  of  the  tube  will  naturally  take  place  principally 
in  the  side  walls  or  lateral  plates  of  the  formed  tube;  second,  that  the  primary 
connection  between  the  two  side  walls  is  the  ventral  median  plate,  the  dorsal 
median  plate  having  been  produced  by  a  secondary  fusion.  This  being  the 
case,  the  ventral  connection  between  the  two  lateral  plates  will  naturally  be 
more  extensive  and  possibly  more  primitive  than  the  dorsal.  The  ventral  and 
dorsal  median  plates  do  not  usually  develop  nervous  tissue,  but  bands  of  vertical 
elongated  ependyma  cells.  In  places  the  roof  plate  expands  into  thin  mem- 
branes which  are  covered  with  vascular  mesodermal  tissue  forming  chorioid 
plexuses,  such  as  the  chorioid  plexuses  of  the  lateral,  third  and  fourth  ventricles 
(Fig.  408). 


FIG.  400. — Scheme  of  a  median  sagittal  section  through  a  vertebrate  brain  before 

the  closure  of  the  neuropore.     -von  Kupffer. 

A.,  Archencephalon;  D.,  deuterencephalon;  Ms.,  medulla  spinalis  (spinal  cord);  cd.,  notochord; 
en.,  neuronteric  canal;  ek.,  ectoderm;  en.,  entodernv  /.,  infundibulum;  rip.,  neuropore;  pv.t 
ventral  cephalic  fold;  tp.,  tuberculum  posterius. 

It  has  already  been  seen  that  even  at  its  first  appearance  the  neural  plate 
exhibits  a  differentiation  into  an  anterior  expanded  part,  the  brain,  and  a 
posterior  narrower  part,  the  spinal  cord.  After  closure,  in  many  Vertebrates  at 
least,  a  three-fold  division  can  be  made  out:  (i)  A  caudal  part  of  the  neural 
tube,  the  spinal  cord,  which  gradually  expands  cranially  into  (2)  the  caudal  part 
of  the  brain  (deuterencephalon,  v.  Kupffer)  (Fig.  400).  These  two  parts  lie 
above  the  notochord  and  all  the  typical  cerebrospinal  nerves  are  connected 
with  them.  (3)  Cranially,  at  the  anterior  end  of  the  notochord,  the  brain  wall 
expands  ventrally  forming  the  third  portion  (archencephalon) .  At  the  forward 
extremity  is  seen  the  anterior  neuropore.  The  deuterencephalon  is  thus  an 
epichordal  part  of  the  brain,  while  the  archencephalon  is  prechordal.  At  the 
boundary  between  the  two  is  a  ventral  infolding  of  the  brain  wall — the  ventral 
cephalic  fold  (plica  encephali  ventralis) .  At  this  stage  the  brain  resembles  that 
of  Amphioxus  in  many  respects.  From  each  side  wall  of  the  archencephalon 


THE  NERVOUS   SYSTEM. 


461 


an  evagination  appears,  the  optic  vesicle  (Fig.  414)  which  develops  into  the 
retina  and  optic  nerve. 

In  the  next  stage  (Fig.  401),  there  is  a  tendency  for  the  neural  tube  to  bend 
ventrally  around  the  anterior  end  of  the  notochord.  This  bending  is  the 
cephalic  flexure.  At  the  same  time  the  dorsal  wall  above  the  cephalic  fold  be- 
comes expanded  and  is  marked  off  from  that  part  of  the  dorsal  wall  lying 
caudally  by  a  transverse  constriction,  the  rhombo-mesencephalic  fold,  and  from 
the  part  of  the  dorsal  wall  lying  cranially  by  another  transverse  fold  at  the 
site  of  the  future  posterior  commissure.  The  middle  part  of  the  brain,  the 
roof  of  which  is  thus  marked  off,  is  the  mid-brain  or  mesencephalon.  Its 
floor  is  the  middle  projecting  part  of  the  ventral  cephalic  fold.  The  cephalic 
expansion  of  the  brain,  practically  the  former  archencephalon,  is  now  the 


ek. 


U. 


FIG.  401. — Scheme  of  a  median  sagittal  section  through  a.  vertebrate  brain  after  the  formation 

of  the  three  primary  brain  expansions,     von  Kupfier. 
P..  prosencephalon;  M.,  mesencepha'on;  R.,  rhombencephalon;  Ms.,  spinal  cord;  cw.,  chiasma  emi- 
nence; J.,  infundibulum;  It.,  lamina  terminalis;    pv.,  ventral  cephalic  fold;  pn.,  processus 
neuroporicus;  pr.,  rhombo-mesencephalic  fold;  r.1,  unpaired  olfactory  placode;  ro.,  recessus 
(pras-?)  opticus;  (p.,  tuberculum  posterius. 


fore-brain  or  prosencephalon  and  the  caudal  expansion  is  the  rhombic  brain  or 
rho  mbencephalon. 

These  three  primary  brain  expansions  ("vesicles  ")>  the  fore-brain,  mid- 
brain  and  rhombic  brain,  are  constant  throughout  the  Vertebrates.  Beginning 
at  the  location  of  the  former  neuropore  (processus  neuroporicus)  and  passing 
caudally  along  the  floor  of  the  fore-brain  we  have  the  lamina  terminalis  or  end- 
wall  of  the  brain,  containing  a  thickening  which  indicates  the  site  of  the  future 
anterior  (cerebral)  commissure,  next  the  recessus  pr&opticus,  then  another  thick- 
ening, the  chiasma  eminence,  and  finally  a  diverticulum,  the  recessus  postoplicus 
and  infundibulum  (Fig.  401). 

At  a  later  stage  (Fig.  402),  there  appear  two  evaginations  in  the  roof  of  the 
fore-brain,  the  anterior  epiphysis  or  paraphysis  and  the  posterior  epiphysis  or 
epiphysis  proper  (pineal  body).  Immediately  caudal  to  the  paraphysis  is  a 
transverse  infolding  of  the  brain  roof,  the  velum  transversum.  The  line  ad 


462 


TEXT-BOOK  OF  EMBRYOLOGY. 


(Fig.  402)  extending  from  this  fold  to  the  optic  recess  indicates  the  location  of  a 
fold  in  the  side  walls  in  some  forms  and  is  taken  by  some  as  the  boundary  be- 
tween two  subdivisions  of  the  fore-brain,  the  end-brain  or  telenccphalon  and  the 
inter-brain  or  diencephalon.  Cranial  to  the  epiphysis  proper,  is  a  commissure 
in  the  dorsal  wall  (commissura  habenularis}  connecting  two  structures  which 
develop  in  the  crests  of  the  side  walls,  the  ganglia  habenulce. 

From  the  dorsal  part  of  the  telencephalon  is  developed  the  pallium.  The 
ventral  anterior  part  evaginates  toward  the  olfactory  pit,  its  end  receiving  the 
olfactory  fibers.  This  region  is  often  termed  the  rhinencephalon.  Thickenings 
of  the  basal  lateral  walls  of  the  telencephalon  form  the  corpora  striata. 


cp 


pn 


FIG.  402. — Scheme  of  a  median  sagittal  section  through  a  vertebrate  brain  showing 

the  five-fold  division  of  the  brain,  von  Ktipffer. 
T.,  Telencephalon;  D.,  diencephalon;  M.,  mesencephalon;  Mt.,  metencephalon;  Ml.,  myelence- 
phalon;  c.,  cerebellum;  cc.,  cerebellar  commissure;  ch.,  habenular  commissure;  cp.,  posterior 
commissure;  cw.,  chiasma  eminence;  e.,  epiphysis;  e1.,  paraphysis;  J.,  infundibulum;  It., 
lamina  terminalis;  pn.,  processusneuroporicus;  pr.,  rhombo-mesencephalic  fold;  pv.,  ventral 
cephalic  fold;  ro.,  recessus  (prae-)  opticus;  si.,  sulcus  intraencephalicus  posterior;  (p..  tuber- 
culum  posterius.  The  lines  aa.,  dd  and  ff  indicate  the  boundaries  between  four  divisions. 

The  roof  of  the  mesencephalon  finally  develops  the  "optic  lobes."  The 
thickened  part  of  the  roof  lying  immediately  caudal  to  the  rhombo-mesen- 
cephalic fold  develops  into  the  cerebellum.  The  part  of  the  tube  of  which  this 
forms  the  roof  is  often  called  the  hind-brain  or  metencephalon,  while  the  rest  of  the 
rhombencephalon  is  then  termed  the  after-brain  or  myelencephalon.  The  roof  of 
this  portion,  which  has  become  very  thin  in  the  course  of  its  development,  forms 
the  epithelial  part  of  the  tela  chorioidea  of  the  fourth  ventricle.  The  con- 
stricted portion  of  the  tube  between  the  rhombic  brain  and  mid-brain  is  the 
isthmus. 

The  above  subdivisions  of  the  three  primary  expansions  into  five  parts 
(end-,  inter-,  mid-,  hind-  and  after-brains),  especially  the  subdivisions  of  the 
rhombic  brain,  do  not  have  the  morphological  value  of  the  three  primary 


THE  NERVOUS   SYSTEM. 


463 


divisions  but  have  a  certain  value  for  descriptive  purposes.  The  cavities  of 
the  brain  are  the  ventricles  and  their  connecting  passages,  namely,  the  third 
ventricle  of  the  diencephalon  and  the  fourth  ventricle  of  the  rhombencephalon, 
the  two  being  connected  by  the  mid-brain  cavity  (aquceductus  Sylvii}.  The 
telencephalon  usually  develops  a  more  or  less  paired  character,  its  cavities 
being  then  paired  diverticula  of  the  unpaired  fore-brain  cavity  and  known  as 
the  lateral  ventricles. 

Before  the  closure  of  the  brain  part  of  the  neural  tube,  transverse  constric- 
tions appear  across  the  neural  plate.     The  transverse  rings  into  which  the 


-ps. 


FlG.  403. — Chick  embryos;   i,  of  22  hours'  incubation;  2,  of  24  hours;  3,  of  25^  hours;  4,  of  26 

hours,  showing  respectively  2,  5,  6,  and  7  primitive  segments.     Hill. 

cp.,  Caudal  limit  of  fore-brain;  //.,  caudal  limit  of  mid-brain;  «.,  first  primitive  segment; 

ps.,  primitive  streak;  i-n,  neuromeres. 


tube,  when  completed,  is  thus  divided  are  known  as  neuromeres.  They  are 
held  to  represent  a  primitive  segmentation  of  the  head,  similar,  perhaps,  to 
that  exhibited  by  the  spinal  nerves  and  segmental  somatic  musculature  (primi- 
tive segments)  of  the  trunk.  The  neuromeres  may  appear  before  the  head 
somites.  To  what  extent  they  correspond  to  the  somites  or  to  the  visceral 
segmentation  (p.  467)  and  also  to  the  cranial  nerves  is  a  matter  of  dispute. 
Concerning  their  number  there  have  been  various  views,  the  evidence  inclining 
to  three  in  the  fore-brain,  two  in  the  mid-brain  and  six  in  the  rhombic  brain 
(Fig.  403).  Their  presence  and  number  are  most  in  doubt  in  the  cephalic  end 
of  the  tube,  the  highly  modified  prosencephalon. 
30 


464  TEXT-BOOK  OF  EMBRYOLOGY. 

The  general  features  of  the  vertebrate  nervous  system  which  especially 
illuminate  conditions  met  with  in  the  human  nervous  system  are  the  following: 
(i)  The  correlation  between  the  peripheral  structures  (receptors  and  effectors) 
and  the  nervous  system.  (2)  The  distinction  between  the  epichordal  and  pre- 
chordal  portions  of  the  brain.  The  latter  (fore-brain)  is,  in  accordance  with  its 
anterior  position  (comp.  p.  457),  the  most  highly  modified  part  of  the  neural 
tube.  (3)  The  distinction  between  the  segmental  and  suprasegmental  parts 
of  the  brain  (Adolf  Meyer).*  The  segmental  part  of  the  brain  is  that  portion 
in  more  immediate  connection  with  peripheral  segmental  structures.  Its  epi- 
chordal part  is  spinal-like  and  most  clearly  segmental.  Its  prechordal  part, 
both  as  to  its  peripheral  and  central  portions,  is  so  highly  modified  that  its 
segmental  character  is  more  obscure.  It  and  the  rest  of  the  prechordal  brain 
are  most  conveniently  treated  together  as  fore-brain.  The  suprasegmental 
parts  of  the  brain,  or  higher  coordinating  centers,  are  the  cerebellum,  mid- 
brain  roof  and  the  pallium  (cerebral  hemispheres).  Their  general  functional 
significance  has  been  mentioned  (p.  457).  Some  of  their  general  structural 
characteristics  are :  First,  that  they  are  each  expansions  of  the  dorso-lateral 
walls  of  the  neural  tube;  second,  that  in  them  the  neurone  bodies  are  placed 
externally  and  in  layers  (cortex),  the  nerve  fibers  (white  matter)  lying  within; 
third,  that  each  appears  to  have  originally  had  an  especially  close  relation  with 
some  one  of  the  three  great  sense  organs  of  the  head,  the  olfactory,  visual  or 
acustico-lateral  system;  fourth,  that  each  is  connected  with  the  rest  of  the  brain 
by  bundles  of  centripetal  and  centrifugal  fibers,  and  often  there  are  specialized 
groups  of  neurone  bodies  in  other  parts  of  the  brain  for  the  origin  or  recep- 
tion of  such  bundles.  Each  higher  center  has  also  its  own  system  of  association 
neurones. 

It  will  accordingly  be  most  convenient  to  consider:  (i)  the  spinal  cord,  (2) 
the  segmental  part  of  the  epichordal  brain,  (3)  the  cerebellum,  (4)  the  mid- 
brain  roof,  (5)  the  prosencephalon. 

Spinal  Cord  and  Nerves. 

As  already  brought  out,  there  are  two  principal  morphological  differences 
between  the  afferent  and  efferent  peripheral  neurones.  First,  the  neurone 
bodies  of  the  former  are  located  outside  the  neural  tube,  while  the  neurone 
bodies  of  the  latter  lie  within  the  walls  of  the  neural  tube.  Second,  the  afferent 

*This  distinction  apparently  ignores  the  fact  that  the  primitive  neuromeric  segmentation  of  the  ;' 
neural  tube  involves  its  dorsal  as  well  as  its  ventral  walls  and  thus  "  suprasegmental  "  as  well  as  "  seg-  !i 
mental "  structures  were  originally  segmental.     This  may  be  granted,  but  while  the  demonstration 
of  the  primitive  segmentation  of  the  neural  tube  may  be  valuable  as  showing  the  primitive  mechan- 
ism which  has  undergone  later  modifications,  the  importance  of  such  later  modifications  renders  the 
above  distinction  necessary.     The  main  significance  of  the  nervous  system  is  its  associative  character  i 
and  its  progressive  development  is  not  as  a  segmental,  but  as  a  more  and  more  highly  developed 
associating  mechanism. 


THE  NERVOUS   SYSTEM. 


465 


nerves  enter  the  dorsal  part  of  the  lateral  walls  of  the  tube,  while  the  efferent 
nerves  leave  the  ventral  part  of  the  lateral  walls,  their  neurone  bodies  lying  in 
this  ventral  part.  The  effect  of  this  upon  the  structural  arrangements  within 
the  tube  is  the  production  in  the  tube  of  two  columns  of  neurone  bodies,  a  dorsal 
gray  column  for  the  reception  of  the  dorsal  or  afferent  roots  and  a  ventral 
gray  column  containing  the  efferent  neurone  bodies. 

Another  important  differentiation  arises  apparently  from  the  important 
physiological  difference  in  general  character  between  the  activities  of  what  may 


FIG.  404. — Transverse  section  through  the  body  of  a  typical  Vertebrate,  showing  the  peripheral 

(segmental)  nervous  apparatus.     Froriep. 
Small  dots,  afferent    visceral    neurones;    coarse  dots,  afferent    somatic    neurones;    dashes,  efferent 

visceral  (ventral  root  and  sympathetic)  neurones;  lines,  efferent  somatic  neurones. 
Darm,  gut;    Ggl.  spin.,  spinal  ganglion;    Ggl.  vert.,  vertebral  sympathetic  ganglion;    Ggl.  mesent., 

mesenteric  sympathetic  ganglion.    The  peripheral  sympathetic  ganglionic  plexuses  (Auer- 

bach    and  Meissner)  are  not  shown.     Muse.,  muscle;    Rad.  dors.,  dorsal  root;    Rad.  vent., 

ventral  root;  R.  contm.,  white  ramus  communicans. 
Two  sympathetic  neurones  are  represented  as  intercalated  in  the  visceral  efferent  pathway.     It  is 

doubtful  if  there  should  be  more  than  one. 

be  termed  the  internal  (visceral  or  splanchnic}  and  the  external  (somatic)  struc- 
tures. Internal  activities  are  to  a  certain  extent  independent  of  activities 
which  have  to  do  more  with  the  reactions  of  the  organism  to  the  external  world, 
and  consequently  their  nervous  mechanisms  have  a  more  or  less  independent 
character,  forming  what  is  often  called  the  autonomic  (sympathetic)  system. 
This  independence  is  exhibited  structurally  by  the  intercalation  in  the  per- 
ipheral pathway  of  additional  neurones,  whose  bodies  form  visceral  ganglia 


466  TEXT-BOOK  OF  EMBRYOLOGY. 

connected  in  various  ways  among  themselves  and  probably  having  their  own 
reflex  arcs  or  plexuses.  These  ganglia  are  nevertheless  to  some  extent  under 
the  control  of  the  efferent  neurones  of  the  central  nervous  system,  some  of 
which  send  their  axones  to  such  ganglia  (Fig.  404).  There  are  thus  in  the 
central  nervous  system  two  categories  of  efferent  peripheral  neurones,  those 
innervating  visceral  structures  via  sympathetic  ganglia  and  those  innervating 
somatic  structures.  The  bodies  of  the  somatic  efferent  neurones  are  located 
in  the  ventral  gray  matter  of  the  nerve  tube,  while  the  bodies  of  the  splanchnic 
efferent  neurones  are  believed  to  occupy  more  central  and  lateral  positions  in 
the  lower  half  of  the  gray  matter  of  the  neural  tube  (Fig.  404).  It  is  uncer- 
tain whether  there  are  similar  afferent  splanchnic  neurones  in  the  sympathetic 
ganglia,  and  thus  distinct  from  those  in  the  spinal  ganglia,  or  whether  these  all 
lie  in  the  spinal  ganglia  and  are  consequently  not  fully  differentiated  from  the 
somatic  afferent  neurones. 

The  muscular  segmentation  of  the  trunk  has  already  been  mentioned  and 
also  the  corresponding  segmental  arrangement  of  the  spinal  nerves.  Local 
extensions  of  this  musculature  and  of  its  overlying  cutaneous  surface  in  the 
form  of  fins  and  limbs  cause  corresponding  increase  in  the  size  of  those  seg- 
ments of  the  cord  innervating  them.  This  is  due  to  the  increased  number  of 
afferent  fibers  and  consequent  increase  in  the  dorsal  white  columns  and  in  the 
receptive  dorsal  gray  columns,  also  to  the  increase  in  the  number  of  efferent 
peripheral  neurones  whose  bodies  occupy  the  ventral  gray  column  (e.g.,  cervi- 
cal and  lumbar  enlargements).  (Compare  also  the  differentiation  in  the 
cervical  cord  and  lower  medulla  of  the  columns  and  nuclei  of  Goll  for  the 
lower  extremities  and  those  of  Burdach  for  the  upper  extremities). 

In  general,  the  intermediate  neurones  of  the  cord  fall  into  two  categories; 
intersegmental  (ground  bundles),  connecting  cord  segments,  and  those  send- 
ing long  ascending  bundles  to  suprasegmental  structures  (see  pp.  472  and  473.) 

The  Epichordal  Segmental  Brain  and  Nerves. 

The  principal  peripheral  structures  which  exert  a  determining  influence  on 
the  structure  of  the  epichordal  brain  are :  The  mouth,  the  respiratory  apparatus 
(gills  and  later  lungs),  and  two  specialized  sensory  somatic  structures,  the 
acustico-lateral  system  and  the  optic  apparatus. 

In  the  gills  we  have  essentially  a  series  of  vertical  clefts  forming  communica- 
tions between  the  pharynx  and  the  exterior,  the  intervals  between  the  clefts 
being  the  gill  arches.  The  musculature  of  the  gill  arches  is  morphologically 
splanchnic  (pp.  302  and  311).  The  gill  or  branchial  musculature  is  in  closer 
relations  with  stimuli  from  the  external  world  than  is  the  visceral  musculature 
of  the  body.  As  a  result  of  this  the  former  is  not  of  the  smooth  involuntary 


THE  NERVOUS   SYSTEM.  467 

type,  like  the  visceral  musculature  of  the  body,  but  is  of  the  striated  voluntary 
type,  like  the  somatic  musculature.  The  branchial  receptors  are  naturally 
visceral  in  character  and  there  is  also  in  this  region  a  series  of  specialized 
visceral  receptors,  the  end  buds  of  the  gustatory  system.  The  development  of 
this  whole  specialized  visceral  apparatus  in  this  region  of  the  head  has  appar- 
ently caused  a  corresponding  reduction  of  the  somatic  musculature. 

The  musculature  of  the  mouth  is  also  splanchnic,  the  mouth  itself  being 
regarded  by  many  morphologists  as  a  modified  pair  of  gill  clefts  which  has  re- 
placed an  older  mouth  lying  further  forward  in  the  region  of  the  hypophysis. 
The  existence  of  this  series  of  gill  clefts  has  naturally  caused  a  branchiomeric 
or  splanchnic  segmentation  of  the  musculature  of  this  region  as  opposed  to  the 
somatic  muscular  segmentation  seen  in  the  trunk.  Whether  these  two  kinds 
of  segmentation  correspond  in  this  region  is  uncertain.  (In  this  connection  see 
Fig.  428  and  p.  496.) 

In  the  acustico-lateral  system  three  parts  may  be  distinguished :  (i)  a  remark- 
able series  of  cutaneous  sense  organs,  extending  in  lines  over  the  head  and  body 
and  known  as  the  lateral  line  organs;  (2)  the  vestibule,  including  the  semicircu- 
lar canals;  (3)  the  cochlea  (organ  of  hearing  proper — Corti's  organ).  In  the 
higher  Vertebrates,  the  lateral  line  organs  have  disappeared,  owing  to  a  change 
from  a  water  to  a  land  habitat;  the  labyrinth  has  remained  unchanged,  and 
the  cochlea  has  undergone  a  much  higher  development  and  specialization. 

Regarding  the  optic  apparatus,  it  is  sufficient  to  point  out  here  that  its  motor 
part,  the  eye  muscles,  is  usually  taken  to  represent  the  sole  remaining  somatic 
musculature  belonging  to  the  head  proper. 

The  peripheral  nerves  of  the  epichordal  part  of  the  brain  have  fundamen- 
tally the  same  arrangements  as  the  spinal  nerves,  namely,  the  peripheral  af- 
ferent neurone  bodies  are  separate  from  the  nerve  tube,  forming  ganglia,  while 
the  bodies  of  the  efferent  neurones  are  located  centrally  in  the  morphologically 
ventral  portions  of  the  lateral  walls  of  the  nerve  tube.  There  are,  however, 
important  differences,  clearly  correlated  with  the  peripheral  differentiations  and 
specializations  outlined  above,  and  affecting  the  afferent  and  efferent  nerves. 

First  to  be  considered  is  the  afferent  part  of  the  trigeminus  (Figs.  405  and 
406).  The  peripheral  branches  of  the  ganglion  (semilunar  or  Gasserian 
ganglion)  of  this  nerve  innervate  that  part  of  the  external  (somatic)  surfaces  of 
the  head  (skin  and  stomodaeal  epithelium)  which  have  not  been  encroached 
upon  by  the  spinal  afferent  nerves.  This  nerve  is  accordingly  more  strictly 
comparable  with  the  afferent  spinal  nerves.  The  central  processes  of  the 
semilunar  ganglion  cells,  after  entering  the  brain,  form  a  separate  descending 
bundle,  the  spinal  V.  It  is  interesting  to  note  that  the  terminal  nucleus  of 
this  bundle  of  fibers  is  the  morphological  continuation  in  the  brain  of  the 
dorsal  gray  column  of  the  cord.  The  extensiveness  of  the  area  innervated  by 


468 


TEXT-BOOK  OF  EMBRYOLOGY. 


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THE  NERVOUS   SYSTEM.  459 

the  trigeminus  may  be  partly  due  to  disappearance  or  specialization  of  anterior 
somatic  nerves  and  also  to  the  growth  of  the  head. 

The  organs  of  the  lateral  line  are  innervated  by  a  quite  distinct  system  of 
ganglionated  afferent  nerves  whose  central  connections  are  nearly  identical  with 
those  of  the  acoustic  (Fig.  405).  With  the  disappearance  of  the  lateral  line 
organs  and  the  specialization  of  the  cochlear  part  of  the  ear  vesicle,  there  is  a 
disappearance  of  the  lateral  line  nerves  (comp.  Figs.  405  and  406)  and  a  well- 
marked  division  of  the  acoustic  nerve  into  vestibular  and  cochlear  portions, 
the  former  innervating  the  older  vestibule-semicircular  canal  portion,  the  latter, 
the  more  recent  cochlea.  Centrally,  the  vestibular  nerve  forms  also  a  descend- 
ing bundle  of  fibers  and  has  its  own  more  or  less  specialized  terminal  nuclei. 
The  latter  is  also  true  of  the  cochlear  nerve. 

The  afferent  portions  of  the  facial,  glossopharyngeal  and  vagus  nerves  in- 
nervate the  splanchnic  receptors  of  the  pharyngeal  and  branchial  surfaces  as 
well  as  of  a  large  part  of  the  viscera.  The  facial,  glossopharyngeal  and  vagus 
also  innervate  the  specialized  splanchnic  receptors,  the  gustatory  system  men- 
tioned above.  This  system  of  taste  buds  has  a  very  extensive  development  in 
certain  lower  Vertebrates,  especially  the  Bony  Fishes.  In  the  latter  the 
system  of  nerves  innervating  these  structures  is  naturally  much  more  extensive 
and  its  central  terminations  and  nuclei  cause  important  modifications  of  the 
medulla.  In  Mammals  the  remnants  of  this  system  are  represented  by  the 
taste  buds  in  the  mouth,  the  nerves  innervating  them  being  the  chorda  tympani 
branch  of  the  facial  and  the  lingual  branch  of  the  glossopharyngeal  (Fig.  406). 
The  central  branches  of  the  ganglia  of  these  three  nerves,  after  entering  the 
brain,  form  a  descending  bundle  of  fibers,  the  tractus  solitarius  (or  communis). 

The  somatic  musculature  of  the  head,  as  above  mentioned,  is  usually  taken 
to  be  represented  by  the  eye  muscles  and,  later,  the  tongue  muscles.  The 
tongue  is  one  of  the  newer  structures,  rising  in  importance  with  the  change  to 
a  land  habitat,  and  its  muscles  are  probably  an  invasion  from  the  neck  region 
caudal  to  the  branchial  arches  (p.  322).  The  eye  muscles  are  innervated  by 
the  III,  IV  and  VI  cranial  nerves,  the  tongue  muscles  by  the  XII  which  is  a 
more  recent  addition  to  the  cranial  nerves.  All  of  these  nerves  are  charac- 
terized by  having  their  neurone  bodies  located  in  the  most  medial  (morpholog- 
ically most  ventral)  portions  of  the  lateral  brain  walls,  and  they  all,  except  the 
IV,  emerge  near  the  mid-ventral  line.  In  these  respects  they  resemble  the 
major  or  somatic  part  of  the  ventral  spinal  roots.  (For  illustration  see  Figs. 
427,  405  and  406). 

The  splanchnic  musculature  of  the  jaws  and  the  branchial  arches  is  inner- 
vated by  the  efferent  portions  of  the  V,  VII,  IX,  X  (and  XI).  The  neurone 
bodies  or  nuclei  of  origin  of  these  nerves  lie  more  laterally  than  those  of  the  III, 
IV,  VI  and  XII,  and  their  axones  also  leave  the  nerve  tube  more  laterally 


470 


TEXT-BOOK  OF  EMBRYOLOGY. 


H 


THE  NERVOUS   SYSTEM.  471 

along  with  the  incoming  afferent  fibres.  These  nerves  all  exhibit  a  character- 
istic segmental  arrangement  corresponding  to  that  of  the  gill  clefts.  The 
VII,  IX,  and  the  various  nerves  making  up  the  X,  divide  dorsal  to  the  cor- 
responding gill  clefts  into  prebranchial  and  postbranchial  branches,  also 
giving  off  suprabranchial  branches.  The  efferent  element,  or  component, 
forms  a  part  of  each  postbranchial  branch.  These  relations  are  shown  clearly 
in  the  accompanying  diagrams  (Figs.  405  and  406).  Part  of  the  vagus  also 
innervates  the  viscera  and  this  nerve  is  thus  divisible  into  branchial  and  visceral 
portions. 

Two  peculiarities  may  be  noted  in  regard  to  these  splanchnic  nerves :  First, 
that  the  afferent  portions  have  ganglia  resembling  those  of  the  spinal  nerves; 
second,  that  the  branchial  efferent  portions  consist  simply  of  one  neurone 
proceeding  all  the  way  from  the  nerve  tube  to  the  muscle  innervated,  thus 
resembling  the  somatic  rather  than  the  visceral  nerves  of  the  trunk.  As  al- 
ready noted  (p.  466),  these  nerves  regulate  activities  somatic  in  character  but 
involving  splanchnic  structures.  It  is  thus  seen  that  the  dominating  factor  is 
functional  rather  than  morphological — present  functional  necessities  modify 
those  of  the  past. 

With  the  change  from  a  water  to  a  land  habitat  and  the  accompanying 
disappearance  of  gills  and  appearance  of  lungs,  we  have  various  suppressions 
and  modifications  of  the  branchial  musculature  (Fig.  406).  There  are  two 
striking  specializations  of  the  branchial  musculature.  One  is  the  origin  of 
the  facial  (mimetic)  musculature  in  the  highest  Vertebrates.  This  is  derived 
from  the  muscles  of  the  hyoid  arch,  innervated  naturally  by  extensions  of  the 
facial  nerve.  The  other  is  a  specialization  of  muscles,  probably  of  the  caudal 
branchial  arches,  into  cervico-cranial  muscles  (head-movement),  innervated  by 
what  may  be  considered  a  caudal  extension  of  the  vagus  nerve,  namely,  the 
spinal  accessory  (p.  503).  The  splanchnic  laryngeal  musculature  and  its 
nerves  show  a  certain  degree  of  specialization  (sound-production)  in  higher 
forms.  The  efferent  V  is  naturally  a  large  constant  nerve,  in  correlation  with 
the  uniformly  developed  jaw  musculature  in  all  jaw-bearing  (gnathostome) 
Vertebrates  (Figs.  405  and  406).  These  various  changes  in  peripheral 
structures  are  thus  due  either  to  environmental  influences  or  to  developments 
within  the  central  nervous  system  (p.  457).  One  of  the  most  important  en- 
vironmental influences  is  the  change  from  a  water  to  a  land  habitat.  The 
influence  of  the  central  nervous  system  is  shown  in  the  further  development 
and  specialization  of  a  number  of  peripheral  structures  as  motor  " instru- 
ments "  of  suprasegmental  mechanisms. 

The  effects,  then,  of  the  peripheral  arrangements  upon  the  arrangements 
within  the  neural  tube  are:  (i)  The  formation  of  separate  tracts  and  terminal 
nuclei  for  (a)  the  unspecialized  somatic  afferent  V  nerve  (spinal  V  and  posterior 


472 


TEXT-BOOK  OF  EMBRYOLOGY. 


horn) ;  (b)  the  specialized  somatic  vestibular  nerve  (descending  or  spinal  VIII 
and  various  terminal  nuclei)  and  also  the  cochlear  nerve  and  its  various  termi- 
nal nuclei;  (c)  the  splanchnic  afferent  nerves  (tractus  solitarius  and  its 
terminal  nuclei).  (2)  The  separation  of  the  efferent  neurone  bodies  lying  in  the 
neural  tube  into  two  main  longitudinal  series  of  nuclei  (a)  the  somatic  efferent 
nuclei,  occupying  a  more  medial  position,  their  axones  emerging  from  the  neural 
tube  as  medial  ventral  nerve  roots ;  (b)  the  splanchnic  efferent  nuclei  occupying 
a  more  lateral  position,  their  axones  emerging  laterally  and  forming  mixed 
roots  with  the  incoming  afferent  fibers  (Fig.  407). 


FIG.  407. — Diagram  of  a  transverse  section  through  the  lower  human  medulla  showing  the  origin  of 
the  X  and  XII  cranial  nerves.     Schafer. 

g,  Ganglion  cell  of  afferent  vagus  sending  central  arm  (root  fiber)  to  solitary  tract  (/.  s.)  and  col- 
lateral to  the  nucleus  of  the  solitary  tract  (f.s.n.).  It  is  not  certain  that  the  axones  of  the 
cells  of  this  terminal  nucleus  take  the  course  indicated  in  the  figure,  n.  amb.,  nucleus  am- 
biguus  and  d.  n.  X,  dorsal  efferent  nucleus  of  the  vagus,  both  of  which  send  out  axones  as  the 
efferent  root  fibers  of  the  vagus.  These  two  represent  the  lateral  or  splanchnic  efferent  nuclei 
of  this  region,  n.  XII,  nucleus  of  the  hypoglossus  the  axones  of  which  pass  out  medially  as 
efferent  root  fibers  of  the  XII.  This  nucleus  represents  the  medial  or  somatic  efferent  nuclei 
of  this  region,  f.s..  tractus  solitarius  or  descending  roots  of  vagus,  glossopharyngeus  and 
facial;  d.  V.,  descending  spinal  root  of  the  trigeminus;  r.,  restiform  body;  o.,  inferior  olivary 
nucleus  (''olive");  pyr..  pyramid. 

The  intermediate  neurones  of  the  epichordal  segmental  brain,  as  well  as 
of  the  cord,  fall  into  two  general  systems.  One  of  these  is  the  system  of 
Inter  segmental  neurones,  connecting  various  segments  of  the  segmental  brain 
and  cord.  This  system  may  be  collectively  termed  the  ground  bundles  (of  the 
cord)  and  reticular  formation  (of  the  brain) .  These  neurones  may  be  regarded 
as  not  only  furnishing  the  various  reflex  communications  between  the  afferent 
and  efferent  cerebrospinal  peripheral  neurones,  but  as  also  forming  a  system 
upon  which  the  descending  neurones  from  the  higher  coordinating  centers 
(suprasegmental  structures)  act,  before  the  efferent  peripheral  neurones  are 
reached.  This  system  may  thus  be  regarded  in  general  as  more  closely  associ- 


THE   NERVOUS   SYSTEM.  473 

ated  with  the  efferent  than  with  the  afferent  peripheral  neurones.  Certain 
tracts  in  this  system  and  their  nuclei  of  origin  have  reached  a  considerable 
degree  of  differentiation,  due  principally  to  association  with  higher  centers. 
Among  these  differentiated  reticulo-spinal  tracts  may  be  mentioned  the  medial 
longitudinal  fasciculus,  the  rubro-spinal  tract,  and  the  various  tracts  from 
Deiters'  nucleus.  The  other  system  consists  of  nuclei  which  are  associated 
with  the  afferent  axones  as  their  terminal  nuclei,  the  axones  of  which  form  long 
afferent  tracts  to  suprasegmental  structures.  Especially  well-marked  differ- 
entiations of  nuclei  and  tracts  of  this  system  are  usually  due  both  to  its  con- 
nections with  peripheral  structures  and  with  the  higher  centers.  The  principal 
afferent  suprasegmental  tracts  to  the  cerebellum  are  mentioned  below  (p.  473). 
Those  to  mid-brain  roof  and  (via  added  neurones)  to  pallium  are  the  medial 
fillet  or  lemniscus  from  the  nuclei  of  the  columns  of  Goll  and  Burdach,  the 
lateral  lemniscus  from  the  cochlear  terminal  nuclei  and  other  ascending  tracts 
from  terminal  nuclei  of  peripheral  afferent  neurones. 

The  Cerebellum. 

The  other  great  factor  (see  p.  457)  affecting  the  structure  of  the  epichordal 
brain  is  the  development  in  it  of  two  higher  coordinating  centers  or  supraseg- 
mental structures,  the  cerebellum  and  optic  lobes.  The  cerebellum  is  a  develop- 
ment of  the  dorsal  part  of  the  lateral  walls  of  the  tube  just  caudal  to  the  isthmus 
and  was  probably  primarily  developed  in  correlation  with  the  acustico-lateral 
system,  especially  with  the  lateral  line  and  vestibule-semicircular  canal 
portions  (p.  467).  Due  probably  to  the  fact  that  it  is  thus  an  important 
"equilibrating"  mechanism,  the  cerebellum  has  acquired  other  important  con- 
nections besides  its  original  ones  with  the  acustico-lateral  system.  In  the 
vertebrate  series  it  is  especially  developed  in  all  active  balancing  forms  (Fig.  408) . 
In  Mammals  it  has  acquired  important  connections  with  the  greatly  enlarged 
pallium  (cerebral  hemispheres),  in  accordance  with  its  general  regulative  in- 
fluence (static  and  tonic)  upon  motor  reactions.  The  great  development  of  the 
cerebellum  has  profoundly  modified  the  anatomical  arrangements  of  the  rest  of 
the  brain  and  cord,  owing  to  its  numerous  and  massive  connections.  The  fol- 
lowing important  masses  of  gray  matter  and  fiber  bundles  may  be  mentioned  as 
cerebellar  afferent  connections :  Clarke's  column  cells,  and  other  cells  in  the 
cord,  and  the  spino-cerebellar  tracts;  the  lateral  nuclei,  inferior  olives  and  the 
restiform  body  in  the  medulla;  part  of  the  pes  pedunculi,  the  pontile  nuclei  and 
middle  peduncle  of  the  cerebellum.  The  superior  cerebellar  peduncle  to  the 
red  nucleus,  together  with  tracts  to  Deiter's  nucleus,  belong  to  the  cerebellar 
efferent  connections.  The  cortico-pontile  portion  of  the  pes,  the  pontile  nuclei 
and  the  middle  peduncle  represent  the  most  recently  developed  cerebral  con- 
nections (comp.  pp.  477-479  and  Fig.  409). 


474  TEXT-BOOK  OF  EMBRYOLOGY. 

The  Mid-brain  Roof. 

This  expansion  of  the  dorsal  part  of  the  neural  tube  constitutes  a  higher 
coordinating  center  for  impulses  received  by  various  somatic  nerves — spinal, 
cochlear  and  optic.  Owing  to  its  being,  in  all  forms  below  Mammals,  the 
principal  visual  center,  the  optic  part  (optic  lobes)  varies  in  proportion  to  the 
development  of  the  eye,  animals  with  poorly  developed  eyes  having  small  optic 
lobes.  In  Mammals,  the  optic  part  (anterior  corpora  quadrigemina  or  col- 
liculi)  is  relatively  less  important,  owing  to  a  taking  over  of  a  portion  of  its 
coordinating  functions  by  the  neopallium  (pp.  477,  479),  but  the  cochlear  part 
(posterior  corpora  quadrigemina  or  colliculi)  has  increased  in  importance, 
owing  to  the  rise  of  the  cochlear  organ  (organ  of  Corti).  The  centripetal  and 
centrifugal  connections  of  the  mid-brain  roof  are  not  so  massive  or  extensive 
and  consequently  do  not  modify  the  other  parts  of  the  brain  and  cord  as  pro- 
foundly as  do  those  of  the  cerebellum.  It  sends  descending  tracts  to  after- 
brain  and  cord  segments. 

The  Prosencephalon. 

The  division  of  this  part  of  the  brain  into  the  telencephalon  and  diencephalon 
has  already  been  indicated  (p.  462).  In  the  diencephalon  may  be  noted  (i)  the 
absence  of  the  notochord  ventral  to  the  brain,  thereby  permitting  a  ventral  ex- 
pansion of  the  brain  walls,  the  hypothalamus,  associated  with  an  organ  not 
well  understood,  the  hypophysis;  (2)  certain  more  or  less  vestigial  structures, 
such  as  the  pineal  eyes  (epiphyses),  and  other  primitive  structures,  such  as 
the  ganglia  habenulac,  in  the  dorsal  part,  this  dorsal  portion  being  collectively 
termed  the  epithalamus;  (3)  nuclei  in  (i)  and  (2)  connected  with  olfactory 
and  gustatory  tracts;  (4)  receptive  nuclei  for  the  optic  tract  and  the  cochlear 
path  from  the  posterior  colliculus;  (5)  receptive  nuclei  for  secondary  tracts  from 
the  end  stations  of  more  caudal  somatic  ganglia  (nuclei  of  Goll  and  Burdach 
and  medial  lemniscus).  The  last  two  (4  and  5)  constitute  the  thalamus  and 
increase  in  importance  in  the  higher  Vertebrates  (see  p.  477,  Fig.  409). 

In  the  telencephalon  there  may  be  roughly  distinguished  an  anterior  and  basal 
part,  the  rhinencephalon,  in  especially  intimate  relations  with  the  olfactory  nerve ; 
a  thickening  of  the  basal  wall,  the  corpus  striatum ;  and  a  thinner- walled  dorsal 
part,  the  pallium.  The  latter  may  be  regarded  in  a  sense  as  a  dorsal  develop- 
ment of  the  corpus  striatum  and  first  appears  as  a  distinct  structure  in  the 
Amphibia. 

The  peripheral  or  segmental  apparatus  which  are  connected  with  the  pros- 
encephalon  are  the  highly  modified  optic  and  olfactory  organs.  While  the  optic 
apparatus  primarily  originates  from  the  prechordal  brain,  in  the  lower  Verte- 
brates its  highest  coordinating  center,  as  mentioned  above,  lies  partly  in  the 


THE  NERVOUS   SYSTEM.  475 

epichordal  portion  (optic  lobes).  It  is  possible  that  this  connection  is  secon- 
dary and  contingent  upon  two  functional  necessities,  the  importance  of  cor- 
relation with  stimuli  coming  via  more  caudal  nerves  (cochlear  and  spinal 
nerves),  and  the  innervation  of  its  motor  apparatus  by  epichordal  nerves,  the 
III,  IV  and  VI.  With  the  development  of  the  neopallium  in  Mammals  (see  p. 
477)  and  the  consequent  projection  of  visual  stimuli  upon  it,  the  lower  pre- 
chordal  (thalamic)  centers  form  part  of  the  newer  pathway  to  the  neopallium 
and  thus  increase  in  importance,  while  the  optic  lobes  recede,  assuming  the 
position  of  a  reflex  center,  especially  for  the  visual  motor  apparatus. 

The  olfactory  nerves  enter  the  anterior  extremity  of  the  brain  and  are  con- 
nected by  secondary  and  tertiary  tracts  with  regions  lying  more  caudally,  where 
in  some  cases  the  olfactory  stimuli  are  associated  with  gustatory  and  probably 
with  visual  stimuli.  One  of  these  regions  is  the  hypothalamus  which  receives 
both  olfactory  and  gustatory  tracts  (Herrick) .  More  dorsal  olfactory  pathways 
pass  to  the  epithalamus.  Both  epithalamus  and  hypothalamus  give  rise  to  de- 
scending systems  which  doubtless  ultimately  reach  efferent  nuclei.  In  fact,  this 
part  of  the  brain  presents,  apparently,  a  complicated  primitive  mechanism  for 
the  correlation  especially  of  olfactory  and  gustatory  stimuli,  also  to  some  extent 
of  visual  stimuli  and  stimuli  via  the  trigeminal  nerve,  the  whole  forming  a  sort 
of  oral  sense,  probably  controlling  the  feeding  activities  (Edinger). 

The  next  factor  in  the  further  development  of  this  part  of  the  brain  is  the 
rise  in  importance  of  the  pallium  upon  which  at  first  are  projected  mainly 
olfactory  stimuli  (Fig.  408). 

A  further  and  still  more  extensive  development  of  the  pallium  arises  when 
other  kinds  of  stimuli  are  projected  to  a  considerable  extent  upon  it,  thus  giving 
rise  to  a  distinction  between  the  older  olfactory  pallium  (archipallium)  and  the 
newer  non-olfactory  pallium  (neopallium).  The  latter  appears  first  in  the  lateral 
dorsal  portion  of  the  pallial  wall  and  by  its  subsequent  development  the  archi- 
pallial  wall  is  rolled  inward  upon  the  mesial  surface  of  the  hemispheres. 
Further  changes  consist  in  the  extension  caudally  of  this  portion  pari  passu  with 
the  extension  caudally  of  the  neopallium  and  then  the  practical  obliteration 
of  its  middle  portion  by  the  great  neopallial  commissure,  the  corpus  callosum 
(Fig.  408,  G  and  H). 

In  addition  to  the  increasing  projection  of  stimuli  from  all  parts  of  the  body 
upon  the  neopallium  and  the  consequent  increase  in  centripetal  fiber  termina- 
tions and  in  centrifugal  neurone  bodies  lying  in  its  walls,  a  second  factor  in 
the  development  of  the  neopallium  is  the  enormous  increase  of  its  association 
neurones.  It  is  the  latter  feature  which  especially  distinguishes  the  human 
from  other  mammalian  brains. 

The  biological  significance  of  these  changes  lies  in  the  fact  that  there  is  thus 
produced  a  mechanism  not  only  for  the  association  of  all  kinds  of  stimuli,  but 


476 


TEXT-BOOK  OF  EMBRYOLOGY. 


Q    OftNITHORHYNCHUS 


FIG.  408. — A-F  (Edinger)  are  sagittal  sections  showing  structures  lying  in  the  median  line  and  also 
paired  structures  (e.g.,  pallium)  lying  to  one  side  of  the  median  line.  The  cerebellum  is 
black.  It  is  doubtful  whether  the  membranous  roof  in  A  indicated  as  pallium  is  strictly 
homologous  with  that  structure  in  other  forms  In  B,  Pallium  indicates  prepallial  structures. 

Aq.  Syl.,  Aquaeductus  Sylvii;  Basis  mesen.,  basis  mesencephali;  Bulb,  olf.,  bulbus  olfactorius;  Corp. 
striat.,  corpus  striatum;  Epiph.,  epiphysis;  G.  h.,  ganglion  habenulae;  Hyp.,  hypophysis; 
Infund.,  infundibulum;  Lam.  t.,  lamina  terminalis;  Lob.  elect.,  lobus  electricus;  L.  vagi, 
lobus  vagi;  L.  opt.,  mid-brain  roof;  Med.  obi.,  medulla  oblongata;  Opt.,  optic  nerve;  Pl.chor., 
plexus  chorioideus;  Rec.  inf.,  recessus  infundibuli;  Rec.  mam.,  recessus  mammillaris;  Saccus 
vase.,  saccus  vasculosus;  Sp.  c.,  spinal  cord;  ventr.,  ventricle;  v.  m.  a.,  velum  medullare 
anterius;  v.m.  p.,  velum,  medullare  posterius. 

G  and  H  show  the  mesial  surface  of  the  cerebral  hemispheres  in  a  low  (G)  and  high  (H)  Mammal. 
G.  Elliot  Smith,  Edinger,  slightly  modified. 

The  exposed  gray  matter  of  the  olfactory  regions  is  shaded,  the  darker  shade  indicating  the  archi- 
pallium  (preterminal  area  and  hippocampal  formation),  the  lighter  shade  indicating  the 
rhinencephalon,  which  consists  of  the  anterior  and  the  posterior  (principally  pyriform)  olfactory 


THE  NERVOUS   SYSTEM.  477 

also  for  very  complex  coordinations  between  these  stimuli.  In  this  way  an 
extensive  symbolization  and  formulation  of  individual  experience  (memory, 
language,  etc.)  can  take  place.  The  formulated  experience  of  one  generation 
can  be  immediately  transmitted  (by  education  in  the  broad  sense  of  the  term) 
to  the  plastic  late-developing  neopallia  of  the  next  generation.  In  this 
way  a  racial  experience  may  be  rapidly  built  up  without  the  direct  inter- 
vention of  the  slow  processes  of  heredity  and  natural  selection  and  each  gen- 
eration profit  by  the  accumulated  experience  of  past  generations  to  a  much 
greater  extent.  The  nervous  mechanism,  the  pallium,  is  provided  by  in- 
heritance; experience  is  not  inherited  but  "learned."  The  pallial  associative 
mechanisms  are  continuously  modified  by  their  activities,  thus  affecting  the 
character  of  subsequent  pallial  reactions  (associative  memory).  Such  reac- 
tions are  usually  termed  psychical  or  conscious,  as  distinguished  from  the 
reflex  reactions  of  other  parts  of  the  nervous  system. 

In  the  course  of  these  developments  the  pallium  or  cerebral  hemispheres 
have  enormously  increased  in  size  until  in  man  they  overlap  all  the  other  parts 
of  the  brain.  Naturally  the  extensive  connections  of  the  neopallium  with  the 
rest  of  the  brain  have  profoundly  modified  the  latter.  Among  the  new  struc- 
tures which  have  on  this  account  been  added  to  the  older  structures  of  the  rest  of 
the  brain,  the  following  may  be  mentioned:  (i)  The  centripetal  connections  of 
the  neopallium,  consisting  mainly  of  what  are  usually  termed  the  thalamic  radi- 
ations. These  consist  essentially  of  a  system  of  neurones  passing  from  the 
above  mentioned  termini  in  the  thalamus  of  general  somatic,  acoustic  and  optic 
ascending  systems  to  certain  areas  in  the  cerebral  hemispheres.  In  this  system 
we  can  distinguish  (a)  the  continuation  of  the  fillet  (general  somatic)  to  the  cen- 
tral region  (somsesthetic  area)  of  each  hemisphere;  (b)  the  optic  radiation  from 
the  lower  thalamic  optic  center  (lateral  geniculate  body)  to  the  calcarine 
(visual)  area  of  the  hemisphere;  (c)  the  acoustic  radiation  from  the  medial 
geniculate  body  of  the  thalamus  to  the  upper  temporal  region  (auditory  area) 
of  the  hemisphere.  Associated  with  these  last  two  connections  are  the  increase 

lobes.  In  Amphibia  and  Reptiles  the  hippocampal  formation  includes  all  or  nearly  all  of  the 
mesial  surface.  As  the  early  neopallium  appears  in  the  lateral  hemisphere  walls,  the  neo- 
pallial  commissural  fibers  first  pass  across  the  median  line  in  the  ventral  or  anterior  com- 
missure. With  the  increase  of  the  neopallium  and  its  extension  on  the  mesial  hemisphere 
walls,  its  commissural  fibers  pass  across  more  dorsally  via  the  archipallial  or  fornix  com- 
missure (psalterium)  forming  the  neopallial  commissure  or  corpus  callosum,  the  great  de- 
velopment of  which  nearly  obliterates  the  anterior  hippocampal  formation. 

Com.  ant..  Anterior  commissure;  corp.  callosum,  corpus  callosum;  Fimbr.,  fimbria;  Fiss.  hippo- 
campi, hippocampal  fissure;  Lam.  t.,  lamina  terminalis;  Lob.  olf.  ant.,  anterior  olfactory  lobe; 
Lob.  pymformis,  pyriform  lobe;  Psalt.,  psalterium  (fornix  commissure);  Sept.  pell.,  septum 
pellucidum;  Tub.  olf.,  tuberculum  olfactorium.  Only  a  part  of  the  gray  (cortex)  of  the  hip- 
pocampal formation  appears,  as  the  gyrus  dentatus,  on  the  mesial  surface;  the  remainder  forms 
an  eminence,  the  cornu  Ammonis,  on  the  ventricular  surface.  This  invagination  is  indicated 
externally  by  the  hippocampal  fissure.  The  exposed  fiber  bundle  forming  the  edge  of  this 
formation  (fimbria)  passes  forward  (fornix  and  its  commissure)  and  thence  descends,  as  the 
anterior  pillar  of  the  fornix,  behind  the  anterior  commissure.  The  anterior  pillar  is  partly 
indicated  by  a  few  lines  in  this  region  in  the  figure. 


478 


TEXT-BOOK  OF  EMBRYOLOGY 


FIG.  409. — Principal  afferent  and  efferent  suprasegmental  pathways  (excepting  the  archipallial  con- 
nections, the  efferent  connections  of  the  mid-brain  roof  and  the  olivo-cerebellar  connections). 
Neopallial  connections  are  indicated  by  broken  lines.  Intersegmental  connections  are  omitted. 
Some  peripheral  elements  are  indicated.  Each  neurone  group  (nucleus  and  fasciculus)  is  in- 
dicated by  one  or  several  individual  neurones.  Decussations  of  tracts  are  indicated  by  an  X. 

OC-,  Acoustic    radiation,  from  medial  geniculate  body  to  temporal  lobe;  br.  con}.,  brachium  con- 


THE  NERVOUS  SYSTEM.  479 

of  the  geniculate  bodies  and  the  diminution  of  the  mid-brain  in  importance 
already  alluded  to  (p.  474).  (2)  The  centrifugal  connections  consisting  of  (a) 
the  pyramids  passing  from  the  precentral  area  of  each  hemisphere  to  various 
lower  efferent  neurones,  or  neurones  affecting  the  latter,  and  forming  part  of  the 
internal  capsule  and  pes  pedunculi ;  (b)  fibers  from  various  parts  of  the  hemis- 
phere, forming  the  greater  part  of  the  rest  of  the  internal  capsule  and  pes,  and 
terminating  principally  in  the  pontile  nuclei  whence  a  continuation  of  this 
system  (the  fibers  of  the  middle  peduncle),  passes  to  the  cerebellar  hemisphere. 
The  great  increase  in  size  of  the  cerebellar  hemispheres,  of  the  contained 
nuclei  dentati,  and  probably  of  the  superior  cerebellar  peduncles  are  further 
effects  of  this  new  connection,  which  has  already  been  alluded  to  (see  Cere- 
bellum, p.  473),  (Fig.  409.) 

Another  important  effect  of  the  development  of  the  pallium  is  the  assump- 
tion by  man  of  the  upright  position,  due  both  to  the  specialization  of  the 
hand  to  execute  pallial  coordinations  and  its  consequent  release  from  locomo- 
tion, and  also  to  the  overhanging  of  \he  eyes  by  the  enlarged  cranium.  The 
great  increase  of  cerebellar  connections  may  be  partly  due  to  the  new 
problems  of  equilibrium  connected  with  the  upright  position. 

GENERAL  DEVELOPMENT  OF  THE  HUMAN  NERVOUS  SYSTEM  DURING 

THE  FIRST  MONTH. 

One  of  the  earliest  stages  in  the  development  of  the  human  nervous  system 
is  shown  in  the  2  mm.  embryo  of  about  two  weeks  (Fig.  410).  This  shows 
the  stage  of  the  open  neural  groove.  The  appearance  of  a  transverse  section 
of  the  neural  plate,  groove  and  folds,  in  other  forms,  is  shown  in  Figs.  411 
and  412. 

The  neural  folds  now  become  more  and  more  elevated  and  finally  meet,  thus 
forming  the  neural  tube  as  previously  described  (p.  458).  The  fusion  of  the 
neural  folds  begins  in  the  middle  region  and  thence  extends  cranially  and  cau- 

junctivum  (superior  cerebellar  peduncle);  brack,  pan.,  brachium  pontis  (middle  cerebellar 
peduncle);  b.  q.  i.,  brachium  quadrigeminum  inferias  (a  link  in  the  cochlear  pathway);  e.g. I., 
lateral  or  external  geniculate  body;  c.g.m.,  medial  or  internal  geniculate  body;  c.qtiad.,  cor- 
pora quadrigemina;  f.cort.-sp,,  cortico-spinal  fasciculus  (pyramidal  tract);  /. c.  p.-f.  frontal 
•  cortico-pontile  fasciculus  (from  frontal  lobe) ;  /.  c.-p.t. ,  temporal  cortico-pontile  fasciculus 
(from  temporal  lobe);  /.  c.-p.o.,  occipital  cortico-pontile  fasciculus  (from  occipital  lobe); 
/.  cun.,  fasciculus  cuneatus  (column  of  Burdach);  f.grac.,  fasciculus  gracilis  (column  of 
Goll) ;  /.  s.-t.,  tract  from  cord  to  mid-brain  roof  and  thalamus  (sometimes  included  in  Cowers' 
tract);  f.sp.-c.d.,  dorsal  spino-cerebellar  fasciculus  (tract  of  Flechsig);  f.sp.-c.v.,  ventral 
spino-cerebellar  fasciculus  (tract  of  Cowers,  location  of  cells  in  cord  uncertain) ;  lem.  lat., 
lateral  lemniscus  or  lateral  fillet;  lemniscus'  med.,  medial  lemniscus  or  fillet  (the  part  to  the 
thalamus  is  mainly  a  neopallial  acquisition) ;  n.  each.,  cochlear  nerve;  n.  cun.,  (terminal) 
nucleus  of  the  column  of  Burdach;  n.  grac.,  nucleus  of  the  column  of  Goll;  n.dent.,  nucleus 
dentatus;  n.  opt.,  optic  nerve;  n.r.,  nucleus  ruber  (red  nucleus);  pes  ped.,  pes  peduncu'.i 
(crusta);  pulv.  thai.,  pulvinar  thalami;  pyr.,  pyramid;  rod.  ant.,  ventral  spinal  root;  rod.  post,. 
dorsal  spinal  root;  rod.  opt.,  optic  radiation  (from  lateral  geniculate  body,  and  pulvinar  (?), 
to  calcarine  region);  somaes.,  bundles  from  thalamus  to  postcentral  region  of  neopallium; 
s p. gang.,  spinal  ganglion;  thai.,  thalamus. 

31 


480 


TEXT-BOOK  OF  EMBRYOLOGY. 


dally.  The  stage  of  partial  closure  of  the  neural  tube  is  shown  in  Eternod's 
figure  of  a  human  embryo  of  2.1  mm.  (Fig.  413,  b).  This  order  of  closure  in- 
dicates, to  some  extent,  the  order  of  subsequent  histclogical  development;  the 
extreme  caudal  and  cephalic  extremities  are  more  backward  than  the  parts 
which  close  first.  The  last  point  to  close  anteriorly  marks,  as  stated  previously 
(p.  458),  the  cephalic  extremity  of  the  neural  tube  and  is  the  anterior  neuropore. 
As  indicated  in  Eternod's  embryo,  the  anterior  end  of  the  neural  plate  is  broader 
even  before  its  closure;  thus  when  the  tube  is  completed  its  anterior  end  is  more 
expanded.  This  expansion  is  the  future  brain,  the  narrower  caudal  portion 


Neural  groove 


Belly  stalk 


Chorion- 


FlG.  410. — Dorsal  view  of  human  embryo,  two  millimeters  in  length,  with  yolk  sac. 

von  Spee,  Kollmann. 
The  amnion  is  opened  dorsally. 


being  the  future  spinal  cord.  Before  the  closure  of  the  brain  part  of  the  tube 
the  beginnings  of  the  three  primary  brain  vesicles  are  also  indicated  (Fig.  120). 
At  this  stage  the  neural  plate  shows  no  differentiation  into  nervous  and  sup- 
porting elements.  The  neural  tube  is  composed  of  the  two  lateral  walls  and 
the  median  roof  and  -floor  plates  (comp.  p.  460)  (Figs.  345  and  442). 

The  appearance  of  the  anterior  end  of  the  neural  tube  with  the  closure  com- 
pleted, except  the  anterior  and  posterior  neuropores,  is  shown  in  the  model  of 
one  half  of  the  tube.  The  external  appearance  and  also  the  inner  surfaces  are 
shown  in  Figs.  414  and  415.  At  this  stage  the  cephalic  flexure  (see  p.  461)  is 
already  quite  pronounced,  the  cephalic  end  of  the  brain  tube  being  bent  ven- 


THE  NERVOUS   SYSTEM. 


481 


trally  at  about  a  right  angle  to  the  longitudinal  axis  of  the  remaining  portion  of 
the  tube.  This  bending  begins  before  the  closure  of  the  cephalic  part  of  the 
neural  tube  (Fig.  120).  From  each  side  of  the  brain  near  the  cephalic  ex- 
tremity is  an  evagination  of  the  brain  wall,  the  beginning  of  the  optic  vesicles. 


Neural 
fold 


Ectoderm 


Mesoderm  - 


*       Chorda  anlage  Entoderm 

FIG.  411. — Transverse  section  through  dorsal  part  of  embryo  of  frog  (Rana  fusca). 
x,  Groove  indicating  evagination  to  form  mesoderm. 


Ziegler. 


The  process  of  evagination  and  consequently  the  location  of  the  vesicle  begins 
before  the  closure  of  the  tube. 

Dorsal  and  anterior  to  the  optic  vesicles  can  be  seen  a  slight  unpaired  pro- 
trusion of  the  dorsal  wall,  the  beginning  of  the  pallium.     The  area  basal  to  it  and 


Prim.    Intermed. 
seg.      cell  mass 


Parietal  and 
visceral  mesoderm 


Ectoderm 
(epidermis) 


Chordal 
plate 


Ccelom         Entoderm       Blood  vessels 
FIG.  412. — Transverse  section  of  dog  embryo  with  ten  pairs  of  primitive  segments.     Bonnet. 

extending  a  short  distance  into  the  anterior  wall  of  the  optic  vesicle  is  the  site  of 
the  future  corpus  striatum  (Figs.  414  and  415). 

Caudal  to  the  pallium  and  separated  from  it  by  a  slight  constriction  (in- 
dicated best  by  the  ridge  on  the  inner  wall)  is  another  protrusion  of  the  dorsal 
wall,  the  roof  of  the  diencephalon.  Still  further  caudally  and  separated  from  the 


482 


TEXT-BOOK  OF  EMBRYOLOGY. 


roof  of  the  diencephalon  by  another  slight  constriction  is  another  expansion  of 
the  dorsal  wall,  the  roof  of  the  mid-brain  or  of  the  mesencephalon  which  arches 
over  the  cephalic  flexure.  It  is  separated  by  another  constriction  (plica 
rhombo-mesencephalica)  from  the  rhombic  brain  or  rhombencephalon,  which  latter 
tapers  into  the  cord.  A  ventral  bulging  of  the  rhombencephalon  indicates  the 
future  pons  region  (Figs.  414  and  415). 


Cerebral  plate 


Heart 


Ant.  entrance  to 
prim,  gut  (Ant. 
"Darmpforce") 


Neural  tube 


Post,  entrance  to 
prim,  gut  (Post. 
"Darmpforte") 


Neural  fold 
Neural  groove 


Neural  fold 


FIG.  413. — (a)  Ventral  view;  (b)  dorsal  view  of  human  embryo  with  8  pairs  of  primitive 

segments  (2.11  mm.).     Eternod.     From  models  by  Ziegler. 

In  b  the  amnion  has  been  removed,  merely  the  cut  edge  showing;  in  a  the  yolk  sac  has 

been  removed. 


Even  at  this  early  stage  the  cavity  of  the  caudal  part  of  the  rhombencephalon 
is  expanded  dorsally  due  to  an  expansion  of  the  roof  plate,  which  forms  only  the 
narrow  dorsal  median  part  of  the  rest  of  the  tube.  This  expansion  reaches  its 
maximum  about  opposite  the  auditory  vesicle. 

The  principal  changes  in  form  during  the  next  two  weeks  are  the  following 
(Figs.  416  and  472):  The  cephalic  flexure  becomes  still  more  pronounced  so 
that  the  anterior  end  of  the  neural  tube  is  folded  back  upon  the  ventral  side  of 
the  rest  of  the  brain,  an  effect  probably  enhanced  by  the  expansion  of  the 


THE   NERVOUS   SYSTEM. 


483 


FIG.  414. — Lateral  view  of  the  outside  of  a  model  of  the  brain  of  a  human 
embryo  two  weeks  old.     His. 

Diencephalon  Pallium 


Mesencephalon 


Rhombq- 
mesencephalic  fold 


Rhombencephalon 


Neuropore 
Corpus  striatum 
P.  f. 
Optic  evagination 


Ventral  cephalic  fold 
(Seesel's  pocket) 


Pons  region 


FIG.  415. — Lateral  view  of  inner  side  of  the  same  model  shown  in  Fig.  414.     His. 
P.f.  is  the  ridge  corresponding  to  the  peduncular  furrow  on  the  outer  side. 


484  TEXT-BOOK  OF  EMBRYOLOGY. 

ventral  wall  of  the  anterior  portion  (Figs.  416  and  472).  In  the  space  thus 
enclosed  the  dorsum  sellse  is  subsequently  formed.  Associated  with  this 
increase  of  the  cephalic  flexure  is  an  increased  prominence  of  the  mid-brain 
roof.  The  pontine  flexure  has  begun,  there  being  now  a  bending  of  the  whole 
tube  in  the  pons  region,  the  concavity  of  the  bend  being  dorsal.  At  the  same 
time  there  is  a  corresponding  tendency  for  the  roof  of  the  rhombencephalon  to 
become  shorter  and  wider.  There  is  also  a  further  thinning  of  the  above 
mentioned  expanded  portion  of  the  roof  plate  in  this  region,  and  associated 
with  this  a  thrusting  of  the  thick  lateral  walls  outward  at  the  top  so  that  they 
come  to  lie  almost  flat  instead  of  vertically  as  in  the  cord.  From  the  cord 
to  the  place  of  greatest  width  above  mentioned,  this  dorsal  thrusting  apart 


FIG.  416. — Profile  view  of  a  model  of  the  brain  of  a  human  embryo  during  the  third  week.    His. 
A,  Optic  vesicle;  A.v.,  auditory  vesicle;  Br,  pons  region;  H,  pallium;  Hh:  cerebellum;  /,  isthmus; 
M,  mid-brain;  N  and  /?/,  medulla;  NK,  cervical  flexure;  Pm,  mammillary   region;  Tr,  in- 
fundibulum;  Z,  inter-brain  or  diencephalon. 

of  the  lateral  rhombic  walls  obviously  becomes  more  and  more  pronounced. 
In  front  of  this  region  of  greatest  wridth,  the  roof  plate  becomes  narrower  and 
the  dorsal  parts  of  the  walls  (alar  plates)  form  the  rudiment  of  the  cerebellum, 
the  rest  of  the  rhombic  brain  forming  the  medulla  oblongata.  Each  lateral 
wall  of  the  rhombic  brain  is  now  divided  into  a  dorsal  longitudinal  zone  or 
plate  (alar  plate}  and  a  ventral  zone  or  plate  (basal  plate]  by  a  longitudinal 
furrow  along  its  inner  surface,  the  sulcus  limitans.  A  study  of  the  external 
appearances  and  transverse  sections  of  this  part  of  the  brain  tube  will  make 
these  relations  clear  (Figs.  456,  436  to  439  and  427).  Neuromeres  are  also 
present  at  this  stage  (see  p.  496).  In  the  meantime  the  neural  tube  has  also 
become  bent  ventrally  at  the  junction  of  the  brain  and  cord,  forming  the  cervical 


THE  NERVOUS   SYSTEM.  435 

flexure.  The  pallium  has  increased  in  size  and  now  forms  a  considerable 
prominence  on  the  brain  tube.  Its  boundaries  are  also  much  more  clearly 
marked  off  (see  Fig.  471).  On  the  inner  side  of  the  tube,  the  area  below 
the  bulging  of  the  pallium  is  the  corpus  striatum.  Externally,  just  below  the 
bulging,  we  have  the  region  where  the  olfactory  lobes  are  differentiated.  The 
proximal  part  of  the  optic  evagination  has  become  longer  and  narrower.  The 
ventral  expansion  of  the  diencephalon  is  the  hypothalamus,  the  portion  of  the 
diencephalon  dorsal  to  the  latter  being  the  thalamus.  Two  slight  protrusions 
of  the  ventral  wall  of  the  hypothalamus  have  appeared;  the  caudal  one  is  the 
mammillary  region,  the  anterior  one  the  infundibulum.  The  cavity  of  the 
diencephalon  (third  "ventricle)  is  connected  by  the  mid-brain  cavity  (iter  or 
aqiuzduclus  Svlvii)  with  the  rhombic  brain  cavity  or  fourth  ventricle. 

HISTOGENESIS  OF  THE  NERVOUS  SYSTEM. 

The  neural  plate  is  at  first  a  simple  columnar  epithelium.  The  various 
processes  by  which  this  is  converted  into  the  fully  formed  nervous  system  are: 
(i)  cell  proliferation;  (2)  cell  migration;  (3)  cell  differentiation.  These  proc- 
esses are  not  entirely  successive  in  point  of  time,  but  overlap  each  other.  Cell 
division  is  present  from  the  first,  increases  to  a  certain  period  in  development 
and  then  practically  ceases;  cell  migration  is  partly  a  necessary  concomitant  and 
resultant  of  cell  division,  and  cell  differentiation  is  in  part  due  to  the  growth  of 
the  cytoplasm  and  is  in  part  a  result  of  environmental  differences  produced  by 
these  processes.  In  development  the  following  stages  may  be  distinguished: 

(i)  Stage  of  indifferent  epithelium;  (2)  appearance  of  nerve  elements 
(neurones)  and  resulting  differentiation  into  supporting  and  nerve  elements; 
(3)  growth  of  neurones  and  resulting  differentiation  and  development  of  (a) 
peripheral  neurones,  (b)  lower  intermediate  or  intersegmental  neurones,  (c) 
neurones  of  higher  centers  and  neurone  groups  in  connection  with  them  (supra- 
segmental  neurones).  These  stages  do  not  occur  simultaneously  throughout  the 
whole  neural  tube,  some  parts  being  more  backward  in  development  than  others 
(p.  480) .  In  general  the  spinal  cord  and  epichordal  segmental  brain  are  most 
advanced  in  development.  Furthermore,  the  ventral  part  of  the  brain  tube 
precedes  the  dorsal.  The  most  backward  part  of  the  whole  neural  tube  is  the 
pallium. 

The  various  phases  of  /orw-differentiation  of  the  neurone  are  (i)  the 
development  of  the  axone  and,  later,  of  its  branches;  (2)  the  growth  of  the 
dendrites;  (3)  the  formation  of  accessory  coverings  or  sheaths,  the  neurilemma 
and  the  myelin  (medullary)  sheath.  The  principal  internal  differentiations 
are  (i)  the  appearance  of  the  neurofibrils;  (2)  the  .chromophilic  bodies  of 
Nissl;  (3)  pigment.  These  latter  may  all  be  regarded  as  products  of  the 
nucleus  and  undifferentiated  cytoplasm  of  the  nerve-cell. 


486  TEXT-BOOK  OF  EMBRYOLOGY. 

Epithelial  Stage.     Development  of  Neuroglia. 

From  the  very  first,  the  neural  plate  exhibits  dividing  cells  similar  to  those 
seen  in  the  non-neural  ectoderm.  The  cell  divisions  are  indirect  and  the 
mitoses  are  confined  to  the  outer  part  of  the  ectoderm,  occurring  between  the 
outer  ends  of  the  resting  epithelial  cells  (Fig.  417).  These  dividing  cells  have 
been  termed  by  His  germinal  cells.  When  the  neural  tube  is  formed,  the 
mitoses  are  still  confined  to  the  outer,  now  the  luminal,  surface,  this  being  a 
general  phenomenon  in  developing  epithelial  tubular  structures.  As  a  result 
the  daughter  nuclei  migrate  away  from  the  lumen. 

In  the  most  advanced  parts  of  the  neural  tube  (see  p.  485),  the  mitoses  in- 
crease in  number  up  to  about  the  fourth  to  sixth  week  of  development,  and  then 
diminish  and  finally  nearly  disappear  about  at  the  end  of  two  months.  At 
about  the  time  the  blood  vessels  penetrate  the  tube,  the  mitoses  are  no  longer 
entirely  confined  to  the  proximity  of  the  lumen. 

As  a  result  of  proliferation,  the  epithelial  wall  very  early  assumes  the  ap- 
pearance of  a  stratified  epithelium — at  least  there  are  several  strata  of  nuclei. 
There  are  at  this  stage  in  many  forms  two  layers,  an  outer  or  marginal  layer, 
free  of  nuclei,  and  an  inner  or  nuclear  layer  (Figs.  418  and  419).  In  a  human 
embryo,  however,  of  about  two  weeks  this  division  into  layers  is  yet  hardly 
evident,  though  there  are  several  strata  of  nuclei.  Apparently  these  layers  are 
not  well-marked  until  the  radial  arrangement  of  the  myelospongium,  as 
described  below,  has  become  more  pronounced. 

Accompanying  the  above  changes,  changes  also  manifest  themselves  in  the 
character  of  the  cells.  At  about  the  time  of  the  closure  of  the  neural  tube,  the 
cell  boundaries  become  indistinct  and  finally  practically  obliterated,  thus  form- 
ing a  syncytium,  the  myelospongium.  At  the  same  time,  the  syncytium  becomes 
very  alveolar  in  structure  and  a  general  spongioplasmic  reticulum  is  formed  (Figs. 
418  and  419)  by  the  anastomosing  denser  strands  (trabeculse)  of  protoplasm. 
At  a  very  early  stage  (two  weeks),  these  trabeculae  unite  along  the  inner  and 
outer  walls  of  the  neural  tube  forming  internal  and  external  limiting  mem- 
branes. The  nuclei  of  the  neural  tube  have  at  first  an  irregular  arrangement 
in  the  reticulum,  at  least  in  the  human  embryo.  This  is  followed  by  a  more 
radial  arrangement  of  both  nuclei  and  protoplasmic  filaments  (Fig.  420) ,  form- 
ing nucleated  radial  masses  of  protoplasm — the  sponglioblasts  (Figs.  419  to 
422).  There  is  some  dispute  as  to  the  loss,  complete  or  incomplete,  of  identity 
of  the  epithelial  cells  in  the  formation  of  the  spongioblasts.  According  to 
Hardesty,  they  are  formed  by  a  collapse  of  the  epithelial  cells  and  a  rearrange- 
ment of  their  denser  parts  into  axial  filaments.  The  radial  arrangement  does 
not  extend  into  the  outer  part  of  the  neural  tube  which,  retaining  its  irregular 
reticular  character,  is  now  non-nucleated  in  the  human  embryo  and  forms  the 


THE  NERVOUS   SYSTEM. 


487 


FIG.  417. 


FIG.  418. 


mle 


mli 


FIG.  419. 


mle 


a 


FIG.  420. 


FIG.  417.  —  From  the  neural  tube  of  an  embryo  rabbit  shortly  before  the  closure  of  the  tube,     g,  Germi- 

nal or  dividing  cell;  m,  peripheral  zone,  position  of  the  later  marginal  layer.     Jfw. 
FIG.  418.  —  Pig  of  5  mm.,  unflexed.     Just  after  closure  of  the  neural  tube.     Segment  of  a  vertical 

section  of  the  lateral  wall  of  the  tube,     g,  Germinal  cells;  m,  beginning  of  marginal  layer; 

mil,  internal  limiting  membrane;  r,  radial  columns  of  protoplasm.     The  resting  nuclei  lie  in 

the  inner  or  nuclear  layer.     Hardesty. 


488 


TEXT-BOOK  OF    EMBRYOLOGY. 


marginal  layer.  The  increase  in  the  thickness  and  circumference  of  the  walls 
of  the  tube  and  the  resulting  tensions  may  be  a  factor  in  this  arrangement 
of  the  protoplasmic  filaments.  At  the  boundary  between  the  marginal  and 
nuclear  layers  the  reticulum  appears  to  be  especially  dense. 

With  the  further  increase  and  development  of  the  nervous  elements  (see 
p.  492)  the  radial  arrangement  of  the  spongioblasts  noted  above  becomes  more 
and  more  obliterated.  As  shown  by  Golgi  preparations,  in  their  migration  from 
the  lumen  (Fig.  422)  the  spongioblasts  lose  their  connection  with  the  lumen, 


ep      mil 


FIG.  421. — Hardesty.  Combination  drawing  from  sections  of  pig  of  15  mm.  The  upper  part  is 
from  a  section  of  the  same  stage  as  the  lower  but  stained  by  the  Golgi  method.  By  migra- 
tion and  differentiation  the  mantle  layer  has  been  formed.  The  cells  remaining  near  the 
lumen  form  the  ependyma  layer  (ep.).  b,  Boundary  between  mantle  and  marginal  layers; 
ep,  ependyma;  mli  and  mle,  internal  and  external  limiting  membranes;  mv,  differently 
arranged  mid-ventral  portion  of  the  marginal  layer;  r,  radial  filaments;  cs,  connective  tissue 
syncytium. 


their  peripheral  processes  become  abbreviated  and  disappear,  and  they  finally 
differentiate  into  the  irregular  branching  neuroglia  cells  (Fig.  423).  According 
to  Hardesty,  there  is  simply  a  general  nucleated  mass  which  changes  form 
pari  passu  with  changes  in  the  enclosed  differentiating  nervous  elements, 
finally  assuming  shapes  dependent  upon  the  character  of  the  spaces  between 
the  formed  nervous  elements.  An  exception  to  this  is  a  layer  of  nucleated 
elements  which  remain  next  the  lumen  and  form  the  ependyma  cells  which  still 

FIG.  419. — Pig  of   7  mm.,  unflexed.     Segment  from  the  ventro-lateral  wall  of   the  neural  tube; 

g,   Germinal     cells;     mli,   internal    limiting     membrane;    mle,   external   limiting  membrane 

r,  radial,  axial  filaments  of  the  syncytial  protoplasm;  p,  beginning  of  pia  mater.     Hardesty. 
FIG.  420. — Pig  of  10  mm.,  "  crown-rump  "  measurement.     Segment  from  lateral  wall  of  neural  tube. 

b,  boundary  between    nuclear    layer  and    marginal  layer  (m).     Other   references   same   as 

in  419.     Hardesty. 
a  indicates  the  zone  in  which  the  dividing  cells  are  located.     Later,  it  is  composed  of  the  inner  ends 

of  the  ependyma  cells  (column  layer  of  His). 


THE  NERVOUS   SYSTEM. 


489 


490 


TEXT-BOOK  OF  EMBRYOLOGY. 


send  radial  extensions  into  the  wall  of  the  neural  tube  (Figs.  421  and  422). 
These  cells  develop  cilia  projecting  into  the  lumen. 

A  still  later  differentiation  in  the  supporting  elements  of  the  tube  is  the  ap- 
pearance of  neuroglia  fibers — a  product  of  the  spongioblastic  protoplasm,  but 
differing  from  it  chemically  (Fig.  423).  The  exact  relation  of  these  neuroglia 
fibers  to  the  nucleated  neuroglia  cells  in  the  adult  is  a  matter  of  dispute- 


".• 


FIG.  423. — Hardesty.  Combination  drawing  from  transverse  sections  of  the  spinal  cord  of  20  cm. 
pig.  Showing  the  first  appearance  of  neuroglia  fibers,  a,  Neuroglia  cell  as  shown  by  the 
Benda  method  of  staining;  a',  similar  cell  by  the  Golgi  method;  b  and  b',  non-nucleated 
masses;  d,  free  nuclei;  e  and/,  differentiating  neuroglia  fibers;  s,  <:  seal-ring"  cells,  envelop- 
ing myelinating  nerve-fibers. 

With  the  penetration  of  blood  vessels  into  the  neural  tube  a  certain  amount  of 
mesodermal  tissue  is  brought  in.  How  much  of  the  supporting  tissue  of  the 
nervous  system  is  derived  from  the  mesoderm  is  uncertain,  but  it  is  most 
probable  that  it  is  relatively  small  in  amount  and  is  confined  principally  to  the 
connective  tissue  of  the  walls  of  the  blood  vessels. 

Early  Differentiation  of  the  Nerve  Elements. 

It  has  been  seen  that  some  of  the  actively  dividing  cells  (germinal  cells)  at 
first  simply  increase  the  ordinary  epithelial  elements  of  the  tube  which  in  turn 
form  the  myelospongium,  the  spongioblasts  and  finally  the  ependyma  and  the 
neuroglia.  Other  daughter  cells  produced  by  the  division  of  the  germinal  cells 


THE  NERVOUS   SYSTEM. 


491 


differentiate  into  nerve  cells  as  described  below.  Still  others  probably  migrate 
outward  as  indifferent  cells,  which  later  proliferate  and  form  cells  which  differ- 
entiate into  neuroglia  and  nerve  cells. 

According  to  recent  researches  (Cajal),  by  means  of  the  silver  stain  of  Cajal 
the  first  indication  of  the  differentiation  of  cells  into  nerve  cells  is  the  appear- 
ance of  neurofibrils  in  the  cytoplasm  of  cells  near  the  lumen.  The  part  of  the 
cell  in  which  the  neurofibrils  first  appear  is  called  the  fibrillogenous  zone 
(Held)  and  is  usually  in  the  side  furthest  from  the  lumen.  The  cells  in  which 
these  appear  are  apparently  without  processes,  and  are  accordingly  termed 
apolar  cells  (Cajal).  (Fig.  424.) 


FIG.  424. — Section  through  the  wall  of  the  fore-brain  vesicle  of  a  chick  embryo  of  3^  days.     Cajal. 

A,  b  and  c,  Differentiating  nerve  cells  in  apolar  stage,  the  neurofibrils  are  black;  a,  cell  in  a  stage 
transitional  to  the  bipolar  stage;  B,  bipolar  cells;  c  (at  lower  right  corner) ,  cone  of  "  growth  " 
of  developing  axone;  e,  tangential  axone.     The  cells  in  the  bipolar  stage  have  migrated  out 
ward,  but  'the  neuroblast  or  mantle  layer  has  not  yet  been  differentiated. 


The  next  step  in  the  development  of  many,  but  probably  not  all,  of  these  cells 
is  their  transformation  into  bipolar  cells  by  the  outgrowth  of  two  neurofibrillar 
processes,  one  directed  toward  the  lumen,  the  other,  usually  thicker,  toward  the 
periphery,  the  cell  body  at  the  same  time  beginning  to  migrate  outward  (Fig.  424). 
This  bipolar  stage  may  be  regarded  as  conditioned  to  some  extent  by  the  radial 
arrangement  of  the  other  elements,  due  in  turn  partly  to  the  original  epithelial 
structure  and  partly,  possibly,  to  tensions  produced  by  the  growth  of  the  tube. 
It  is  also  interesting  as  recalling  conditions  in  sensory  epithelia  and  in  the 
cerebrospinal  ganglia.  The  bipolar  stage  is  most  common  probably  in  those 
parts  where  the  elements  show  a  radial  arrangement  in  the  adult.  Such  are  the 
layered  cortices  of  the  mid-brain  and  pallium.  Nerve  cells  maintaining  a  con- 
nection, by  central  processes,  with  the  luminal  wall  have  been  described  in  lower 
Vertebrates.  This  connection  may  be  explained  as  due  to  a  persistence  of  the 
central  processes  of  cells  in  the  bipolar  stage. 


492  TEXT-BOOK  OF  EMBRYOLOGY. 

The  next  stage  is  a  monopolar  stage  produced  by  the  atrophy  of  the  luminal 
process.  Cells  in  this  stage  are  the  neuroblasts  of  His,  the  peripheral  processes 
being  the  developing  axones  (Fig.  425).  As  seen  in  ordinary  stains,  the  above 
differentiation  of  the  neuroblasts  is  marked  by  a  corresponding  differentiation 
of  the  nuclear  layer  into  an  inner  layer  retaining  its  previous  characteristic  radial 
arrangement,  and  an  outer  layer  characterized  by  fewer  nuclei  more  irregularly 
arranged.  The  latter  layer  is  the  mantle,  or  neurone  layer  (Fig.  442).  There 
are  now  three  layers :  (i)  inner  (nuclear),  (2)  mantle  (neurone)  and  (3)  marginal. 
The  mantle  layer  is  thus  produced  by  the  migration  and  differentiation  of  cells 
into  neuroblasts.  While  this  process  may  begin  near  the  lumen  (apolar  nerve 


FIG.  425. — Dorsal  portion  of  the  lumbar  cord  of  a  chick  embryo  of  three  days.     Cajal. 
A,  B,  Cells  in  the  apolar  stage  with  fibrillogenous  zones;  B  shows  transition  to  the  bipolar  stage; 
E,  further  advanced  bipolar  cell;  G,  cells  in  monopolar  stage  or  neuroblasts  of  His;  a,  giant 
cone  of  growth.     These  cells  have  migrated  to  the  outer  part  of  the  nuclear  layer,  thereby 
forming  the  beginning  of  the  mantle  layer. 

cell  of  Cajal)  and  progress  as  the  cell  has  moved  somewhat  further  away  (bipolar 
stage),  the  monopolar  stage  is  probably  reached  only  when  such  cells  form  a  part 
of  the  mantle  layer.  In  other  words,  the  mantle  layer  is  created  by  the  migra- 
tion to  a  certain  location  and  differentiation  to  a  certain  stage  of  the  primitive 
nerve  cells.  The  mantle  layer,  as  previously  stated,  probably  also  contains 
indifferent  cells  which  may  by  further  proliferation  and  subsequent  differentia- 
tion become  either  glia  or  nerve  cells.*  The  looser  arrangement  of  the  cells  of  the 
mantle  layer  is  probably  in  some  measure  due  to  the  growth  of  the  dendrites  which 
appear  soon  after  the  axones.  It  may  be  also  due  to  the  beginning  vascularization 
of  the  tissues  with  resulting  transudates  (His)  which  usually,  however,  begins 
somewhat  later.  The  association  in  time  of  vascularization  and  further  growth 

*It  is  an  open  question  as  to  how  late  in  development  these  "  extra  ventricular  "  cell- divisions,  in- 
volving "  indifferent "  cells,  may  occur.  The  neuroglia  cells,  however,  like  other  supporting  elements, 
preserve  this  capacity  of  division  indefinitely,  as  shown  by  the  increase  in  neuroglia  cells  in  patho- 
ogical  conditions. 


THE  NERVOUS   SYSTEM. 


493 


of  neurocytoplasm  (dendrites)  is  significant.  When  the  cell-proliferation  near 
the  lumen  has  ceased,  the  supply  of  new  cells  ceases,  and  as  the  cells  of  the 
inner  layer  continue  to  differentiate  into  cells  of  the  mantle  layer,  the  inner 
layer,  being  no  longer  replenished  from  within,  is  reduced  to  the  single  layer  of 
cells  which  remain  behind  as  ependyma  cells  (p.  488). 


Differentiation  of  the  Peripheral  Neurones  of  Cord  and 
Epichordal  Segmental  Brain. 

Efferent  Peripheral  Neurones.  The  differentiation  of  a  mantle  or 
neurone  layer  from  the  outer  part  of  the  original  nuclear  layer  is  practically 
universal  throughout  the  whole  neural  tube.  It  appears  first  and  is  conse- 
quently most  advanced,  however,  in  the  ventral  part  of  the  lateral  walls  of  the 
cord  and  epichordal  brain.  The  axones  of  neuroblasts  occupying  the  basal  plate 
of  this  region  of  the  neural  tube  grow  out  through  the  external  limiting  mem- 


FIG.  426. — Ventral  part  of  wall  of  lumbar  cord  of  7o-hour  duck  embryo,  showing  efferent  root 

fibers  first  emerging  from  cord  (combined  from  two  sections) .     Cajal. 
A,  Spinal  cord;  B,  perimedullary  space;  C,  meningeal  membrane;  a,  b,  cones  of  radially  directed 

axones;  c,  d,  cones  of  transversely  directed  axones;  D,  bifurcated  cone;  E,  F,  cones  crossing 

perimedullary  space;  C,  aberrant  cones. 

brane  and  emerge  as  the  efferent  ventral  root  fibers.  The  appearance  of  these 
early  root  fibers  in  the  duck  is  shown  in  Fig.  426.  The  process  is  similar  in 
the  human  embryo  and  begins  about  the  third  week.  The  neurones  thus 
differentiated  are  the  efferent  peripheral  neurones. 

In  some  forms,  at  least,  cells  appear  to  migrate  out  from  the  tube  along  with 
the  efferent  root  fibers.  Their  fate  is  not  certain,  but  they  probably  either 
metamorphose  into  the  neurilemma  cells  or  possibly  form  part  of  the  sympa- 
thetic ganglia  (see  p.  499) .  In  general  the  questions  affecting  the  differentiation 


494 


TEXT-BOOK  OF  EMBRYOLOGY. 


of  the  efferent  fibers  are  the  same  as  for  the  afferent  and  are  further  dealt 
with  later  (pp.  499-502). 

The  majority  of  the  efferent  root  fibers  pass  to  the  differentiating  somatic 
muscles  which  they  innervate,  forming  specialized  terminal  arborizations  (the 
motor  end  plates).  The  fibers  to  the  dorsal  musculature  form,  together  with 
the  afferent  fibers  (p.  497),  the  dorsal  branch  of  the  peripheral  spinal  nerve ; 
others  form  part  of  the  ventral  branch  which  sends  a  branch  mesially  toward 
the  aorta.  Some  of  the  fibers  of  the  mesial  branch  take  a  longitudinal  course. 
This  mesial  branch  is  the  white  ramus  communicans  and  terminates  in  the 
various  sympathetic  ganglia  \vhich  are  later  formed  along  its  course  (p.  498). 


FIG.  427. — Diagram  (lateral  view)  of  the  brain  of  a  10.2  mm.  human  embryo  (during  the  fifth  week), 
showing  the  roots  of  the  cranial  nerves.  His. 

Ill,  Oculomotor;  IV,  Trochlear;  V,  Trigeminus  (m,  efferent  root,  s,  afferent  root);  VI,  Abducens; 
VII,  Facial;  VIII,  Acoustic  (c,  cochlear  part,  v,  vestibular  part);  IX,  Glossopharyngeus; 
X,  Vagus;  XI,  Spinal  accessory;  XII,  Hypoglossus.  ot.,  Auditory  vesicle;  Rh.l.,  rhombic 
lip.  The  two  series  of  efferent  roots  (medial  and  lateral)  are  clearly  shown. 


(Comp.  Figs.  263,  265,  432  and  404.)  The  fibers  to  the  sympathetic  ganglia 
are  the  visceral  (splanchnic)  fibers  of  the  ventral  root.  There  are  a  few  other 
fibers  which  grow  dorsally  from  neuroblasts  in  the  ventro-lateral  walls  of  the 
cord  and  thence  out  via  the  dorsal  root  (Fig.  430) .  They  also  are  probably 
visceral. 

In  the  cord  the  splanchnic  fibers,  with  the  exception  above  noted,  issue  with 
the  somatic  fibers  in  a  common  ventral  root.  In  the  epichordal  segmental  brain, 
however,  there  is  a  differentiation  of  the  efferent  neuroblasts  of  the  basal  plate 
into  two  series  of  nuclei,  a  medial  and  a  lateral.  The  medial  series  consists  of 


THE   NERVOUS   SYSTEM. 


495 


the  nuclei  of  the  XII,  VI,  IV  and  III  cranial  nerves,  and  their  axones  grow 
out  as  medial  ventral  root  fibers  (except  the  IV)  (Fig.  427)  to  the  differenti- 
ating muscles  of  the  tongue  and  eyeball  which  they  respectively  innervate. 
These  muscles  are  probably  somatic  and  their  nerves  are  the  somatic  efferent 
cranial  nerves  corresponding  with  the  greater  part  of  the  fibers  of  the  ventral 
roots  of  the  cord  (compare  p.  469) .  The  lateral  series  consists  of  the  nuclei  of 
the  efferent  portions  of  the  roots  of  the  XI,  X,  IX,  VII  and  V  cranial  nerves 
and  their  axones  grow  out  as  lateral  roots  (Fig.  427)  to  the  differentiating 
striated  branchial  (splanchnic)  muscles  (sternocleidomastoideus,  trapezius, 


FIG.  428. — Diagram  of  the  floor  of  the  4th  ventricle  of  a  10  mm.  human  embryo,  illustrating  the 
rhombic  grooves  and  their  relations  to  the  cranial  nerves.  The  point  of  attachment  of  the 
acoustic  and  the  sensory  root  of  the  trigeminal  nerve  is  shown  by  dotted  circles;  the  motor 
nuclei  are  represented  by  heavy  dots.  Streeter. 

pharynx,  larynx,  face  and  jaw)  and  also  to  muscles  of  the  viscera  (via  sympa- 
thetic?). The  lateral  nuclei  and  their  roots  are  thus  splanchnic.  (Cp.  pp. 
302-3,  469,  471.)  Their  root  fibers,  with  the  incoming  afferent  fibers,  form  the 
mixed  roots  of  these  nerves.  The  positions  of  these  various  nuclei  and  their 
roots  are  clearly  indicated  in  Figs.  427,  436-439,  447  and  451  and  require  no 
further  description.  Additional  details  are  mentioned  in  connection  with 
the  afferent  cranial  nerves.  In  the  region  of  the  vagus  nerve,  there  are 
differentiated  two  series  of  lateral  nuclei,  a  ventro-lateral  (nucleus  ambiguus  X) 
and  a  dorso-lateral  (dorsal  efferent  nucleus  X}  (comp.  Fig.  407).  Fig.  452 
32 


496 


TEXT-BOOK  OF  EMBRYOLOGY. 


apparently  indicates  the  beginning  of  this  differentiation.  The  significance 
of  the  dorso-lateral  nucleus  is  uncertain.  It  possibly  sends  fibers  to  the 
sympathetic  system. 

At  about  this  period  six  transverse  rhombic  grooves  are  plainly  marked  in 
the  floor  of  the  fourth  ventricle,  standing  in  relation  with  the  nerves  of  this 
region  (Fig.  428).  They  are  ordinarily  regarded  as  neuromeric,  but  the  above 
relation  would  indicate  that  they  have  primarily  a  branch iomeric  character 
(Streeter).  It  will  be  noticed  that  each  of  the  three  main  ganglionic  masses 
of  this  region  (p.  502)  corresponds  to  two  of  the  grooves.  (Comp.  p.  463). 

The  further  development  of  the  efferent  neurones  exhibits  phases  common 
to  many  other  nerve-cells  with  a  large  amount  of  cytoplasm  (somatochrome 
cells).  The  further  development  of  the  neuro fibrils  of  cell  body  and  dendrites 

Neural  crest 


^s, Ectoderm 

A 

"t Neural 

plate 


Ectoderm 

Neural  crest 


FIG.  429. — Three  stages  in  the  closure  of  the  neural  tube  and  formation  of  the  neural  crest  (spinal 
ganglion  rudiment).  From  transverse  sections  of  a  human  embryo  of  2.5mm.  (13  pairs  of 
primitive  segments,  14—16  days),  von  Lenhossek. 

is,  according  to  some  observations,  at  first  confined  to  the  peripheral  portions, 
leaving  a  clear  zone  in  the  vicinity  of  the  nucleus.  The  chromophilic  sub- 
stance first  appears  as  distinct  granules  about  the  end  of  the  second  month, 
there  being  apparently  a  diffuse  chromophilic  substance  present  before  this 
period.  The  chromophilic  granules  also  are  first  differentiated  in  the  per- 
ipheral portions  of  the  cell.  A  still  later  differentiation  is  the  pigment,  which 
probably  does  not  appear  till  after  birth.  This  increases  greatly  in  amount 
in  later  years  and  is  then  an  indication  of  senility  of  the  nerve-cell. 

Afferent  Peripheral  and  Sympathetic  Neurones. — It  has  already  been 
mentioned  (p.  458)  that  in  the  closure  of  the  neural  tube  certain  cells  forming 
an  intermediate  band  between  the  borders  of  the  neural  plate  and  the  non- 
neural  ectoderm  are  brought  together  by  the  fusion  of  the  lips  of  the  plate 


THE  NERVOUS   SYSTEM. 


497 


and  form  a  ridge  on  the  dorsal  surface  of  the  neural  tube,  this  ridge  being 
known  as  the  neural  crest  (Fig.  429). 

In  the  SPINAL  CORD,  at  three  weeks,  the  neural  crest  has  separatecnrom  the 
cord  and  split  into  two  longitudinal  bands.  The  ventral  border  of  each  band 
shows  a  transverse  segmentation  into  rounded  clumps  of  cells,  forming  the 
rudiments  of  the  spinal  ganglia  which  later  become  completely  separated.  The 
efferent  roots  have  begun  to  develop  but  the  afferent  roots  appear  later  (fourth 
week,  Fig.  434).  The  cells  composing  these  rudiments  are  polyhedral 
or  oval  rather  than  columnar  and  proliferation  still  proceeds  among  them 
A  differentiation  of  these  cells  soon  begins.  Some,  usually  larger  cells 


FIG.  430 — Part  of  a  transverse  section  through  the  cord  and  spinal  ganglion  of  a  56-hour  chick 

embryo  (combined  from  two  sections).     Cajal. 
A,  Efferent  cell  of  dorsal  root;  B,  cone  of  growth  of  central  process  (afferent  dorsal  root  fiber)  of 

spinal  ganglion  cell;  C,  bifurcation  of  afferent  root  fibers  in  cord,  forming  beginning  of  dorsal 

funiculus  or  dorsal  white  column  of  cord. 

begin  to  assume  a  bipolar  shape.  Their  central  processes  grow  toward  the 
dorsal  part  of  the  lateral  walls  (alar  plate)  of  the  neural  tube  which  they  enter 
(Fig.  430),  becoming  afferent  (dorsal)  root  fibers.  These  fibers  enter  the  mar- 
ginal layer  and  there  divide  (Figs.  430  and  441)  into  ascending  and  descend- 
ing longitudinal  arms  which  constitute  the  beginning  of  the  dorsal  (posterior) 
funiculus  of  the  cord.  The  peripheral  processes  of  the  developing  ganglion 
cells  grow  toward  the  periphery,  uniting  with  the  ventral  root  and  forming 
with  it  the  various  branches  of  the  peripheral  spinal  nerve  (compare  Figs. 
263,  265,  432  and  404).  Other  peripheral  branches  pass  as  a  part  of  the 
white  ramus  communicans  to  the  sympathetic  ganglia  through  which  they 


498 


TEXT-BOOK  OF  EMBRYOLOGY. 


proceed  to  the  visceral  receptors.  These  latter  fibers  are  thus  visceral  afferent 
fibers. 

It  is  now  known  that  the  spinal  ganglion  is  a  much  more  complicated  struc- 
ture and  has  more  forms  of  nerve  cells  than  was  formerly  realized.  The  dif- 
ferentiation into  these  various  types  has  not  yet  been  fully  observed.  The 
bipolar  cells,  however,  become  unipolar  in  the  manner  shown  in  Fig.  431. 
The  cell  body  first  becomes  eccentrically  placed  with  reference  to  the  two  proc- 
esses and  then,  as  it  were,  retracts  from  them,  remaining  connected  with  them 
by  a  single  process.  This  change  may  economize  space. 

According  to  most  authorities,  many  of  the  cells  of  the  neural  crest  do  not 
cease  their  migration  by  forming  spinal  ganglia,  but  undifferentiated  cells 


FIG.  431. — Section  of  spinal  ganglion  of  1 2-day  chick  embryo.     Cajal. 

Showing  various  stages  of  the  change  from  the  bipolar  to  the  unipolar  condition.  A,B,  Unipolar 
cells;  C,  D,  F,  G,  cells  in  transitional  stage;  E,  bipolar  cell;  H,  immature  cell.  The  neuro- 
fibrils  are  well  shown. 


wander  still  further  ventralward  and  form,  probably  also  undergoing  still 
further  proliferation,  the  rudiments  of  the  various  sympathetic  ganglia,  becom- 
ing subsequently  differentiated  into  the  sympathetic  cells.  By  this  migration 
there  is  first  formed  a  longitudinal  column  of  cells  ventral  to  the  spinal  ganglia 
(Fig.  433)  and,  later,  in  relation  with  the  white  communicating  rami  (Fig. 
432).  This  column  becomes  segmented  (seventh  week),  forming  ultimately 
the  ganglia  of  the  vertebral  sympathetic  chain.  In  the  meanwhile,  the 
cells  of  the  column  proliferate  in  places,  forming  rudiments  which,  by  migra- 
tion and  further  differentiation,  form  the  ganglia  of  the  various  prevertebral 
sympathetic  plexuses  (cardiac,  cceliac,  pelvic,  etc.).  Further  migrations  lead  to 
the  formation  of  the  ganglia  of  the  peripheral  plexuses  (Auerbach,  Meissner, 


THE  NERVOUS   SYSTEM. 


499 


etc.).  All  these  ganglia,  probably,  are  innervated  by  fibers  from  the  white 
ramus,  along  whose  course  they  apparently  migrated.  The  axones  of  their 
cells  pass  to  visceral  structures  either  in  the  same  segment  or,  via  the  longi- 
tudinal chain,  to  those  of  other  segments.  Some  also  join  the  branches  of 
the  peripheral  spinal  nerves  (gray  ramus).  Fibers  of  the  white  ramus  also  pass 
longitudinally  in  the  chain  to  vertebral  ganglia  of  other  segments.  The 
possibility  previously  mentioned  (p.  493)  of  a  contribution  to  the  sympa- 
thetic ganglia  by  cells  migrating  out  along  with  the  ventral  roots  must  be  kept  in 
mind.  It  would  seem  a  priori  more  probable  that  these  latter  would  furnish 
the  efferent  sympathetic  cells,  but  the  efferent  cells  predominate  in  the  sym- 


Spinal  cord  • 
Spinal  ganglion  • 


Ventral  root 


Mixed  spinal  nerve 
Myotome 


Sympathetic  ganglion t-ji 


FIG.  432. — From  a  transverse  section  of  a  chick  embryo  of  4^  days.     Neumayer. 


pathetic  and  must  thus  be  regarded  as  derived  partly  or  wholly  from  the 
neural  crest  which  furnishes  at  least  the  major  part  of  all  the  sympathetic 
cells. 

It  seems  probable  that  not  all  the  cells  of  the  neural  crest  form  nerve  cells, 
but  some,  usually  smaller  cells,  become  closely  applied  to  the  spinal  ganglion 
cells,  forming  amphicyies,  while  others  (lemmocytes)  wander  out  along  the  nerve 
fibers  and  become  the  neurilemma  cells,  forming  the  neurilemma.  These  cells 
in  this  case  would  be  quite  strictly  comparable  to  the  glia  cells  of  the  neural 
tube.  According  to  another  view,  the  neurilemma  cells  are  of  mesodermal 
origin.  While  this  point  cannot  be  considered  entirely  determined,  it  seems 
fairly  certain  that  in  some  types  at  least  the  former  view  is  correct,  removal  of 
the.  neural  crest  having  resulted  in  the  formation  of  efferent  nerves  without 


500 


TEXT-BOOK  OF  EMBRYOLOGY. 


neurilemma  cells  (Harrison).  The  modification  into  neurilemma  cells  seems 
to  be  accomplished  by  their  enveloping  the  axones  and  becoming  closely 
applied  to  them. 

The  peripheral  nerve  grows  toward  the  periphery  as  a  bundle  of  fibers  which  forms,  as 
seen  in  many  stains,  a  common  fibrillated  mass,  dividing  at  its  extremity  into  the  develop- 
ing branches  of  the  nerve.  The  lemmocytes  closely  envelop  each  of  these  growing  tips, 
but  proximally  only  envelop  the  main  nerve  trunk  (Bardeen).  The  final  clear  separation  of 


Notochord 


Spinal  ganglion  rudiment 


-Sympathetic  ganglion  rudiment 


FlG.  433. — From  a  transverse  section  through  a  shark  (Scyllium)  embryo  of  15  mm.,  showing  the 

origin  of  the  sympathetic  ganglion.     Onodi. 

In  mammals  the  cells  are  more  scattered  and  their  origin  from  the  spinal  ganglion 
rudiment  not  so  clear. 

the  fibrillated  mass  into  the  individual  nerve  fibers  is  accomplished,  according  to  Gurwitsch, 
by  these  accompanying  cells  forming  septa  within  the  mass  and  finally  enveloping  each 
axone  as  its  neurilemma  sheath.  Growth  in  bundles  appears  to  be  characteristic  also  of  the 
axones  (tracts  and  fasciculi)  of  many  neurone  groups  in  the  central  nervous  system. 

Owing  to  the  presence  of  these  migrating  cells  as  well  as  of  mesodermal  cells, 
the  peripheral  nerves  in  their  earlier  stages  appear  cellular  in  character;  later  the 
fibrous  elements  predominate,  the  nuclei  becoming  more  scattered  and  changing 
into  the  flatter  nuclei  characteristic  of  the  neurilemma  (Fig.  432).  According  to 
one  view  (Balfour),  the  nerve  fibers  themselves,  are  differentiated  from  the  cyto- 


THE  NERVOUS   SYSTEM.  501 

plasm  of  these  cell-strings  and  are  thus  multicellular  structures.  Still  another 
view  is  that  of  Hensen,  according  to  which  the  fibers  are  a  differentiation  in 
situ  from  preexisting  syncytial  bridges  uniting  the  parts  connected  subsequently 
by  the  formed  nerve  fibers.  This  differentiation  may  not  be  primarily  con- 
nected with  the  neuroblasts  (Apathy,  Paton).  An  intermediate  view  between 
this  and  the  outgrowth  view  of  His  is  that  of  Held,  according  to  which  the 
neurofibrillar  substance  is  an  outgrowth  from  the  neuroblast  body,  or  at  least  a 
differentiation  proceeding  from  that  body,  but  always  within  the  preexisting 
cellular  bridges  of  Hensen.  The  differentiating  fiber  is  thus  always  intracel- 
lular  instead  of  intercellular  as  according  to  the  His-Cajal  view.  The  experi- 
ments of  Harrison  above  alluded  to,  in  which  the  accompanying  migrating  cells 
were  eliminated  and  naked  axones  (axis-cylinders)  nevertheless  developed,  ap- 
parently disposes  of  the  cell-string  theory  of  Balfour.  The  growth  of  the 
fibers  in  the  marginal  layer  of  the  central  nervous  system  is  also  unfavorable  to 
this  theory.  The  apparently  proven  capacity  of  growing  axones  to  find  their 
way  through  foreign  tissues  (aberrant  regenerating  nerve  fibers,  Cajal), 
through  ventricular  fluid  (Cajal),  and  even  through  serum  (Harrison)  seems  to 
throw  the  weight  of  evidence  in  favor  of  the  view  of  His.  The  latter  is  the 
view  adopted  in  this  description,  though  many  of  the  most  important  facts  of 
development  are  not  perhaps  entirely  irreconcilable  with  any  of  these  views. 
The  general  conception  of  the  neurone  is  affected  by  these  questions  and  the 
related  question  of  anastomoses  between  the  nervous  elements,  whether  present 
at  all,  and  if  present,  whether  primary  or  secondarily  acquired. 

From  the  above  it  would  seem  that  the  cells  of  the  neural  crest  have  the 
capacity  of  differentiating  into  afferent  neurones,  efferent  (sympathetic)  neurones 
and  supporting  cells.  Other  cells  of  the  neural  crest  differentiate  into  the 
chromafnne  cells  of  the  suprarenal  glands  and  similar  structures  (p.  430). 

There  are  several  views  as  to  the  development  of  the  myelin  sheath.  Ac- 
cording to  one  view  (Vignal),  it  is  a  product  of  the  neurilemma  cells,  being 
formed  in  a  manner  analogous  to  the  formation  of  fat  by  fat  cells.  Accord- 
ing to  Wlassak,  the  various  substances  composing  the  myelin  (fat,  lecithin 
and  protagon)  are  first  found  in  the  central  nervous  system  in  the  protoplasm 
of  the  spongioblasts,  their  probable  original  source  being  the  blood  of  the 
meningeal  blood  vessels.  Later,  the  myelin  is  laid  down  around  the  axones, 
appearing  first  as  drops  or  granules.  The  same  process  takes  place  in  the 
peripheral  nervous  system.  The  supporting  elements  of  the  nervous  system 
thus  would  have  a  chemical  as  well  as  a  mechanical  function.  Another  view 
(Gurwitsch)  is  that  the  myelin  is  a  product  of  the  axone  and  is,  at  its  first 
appearance,  quite  distinct  from  the  neurilemma  cells. 

As  the  appearance  of  the  myelin  sheath  is  a  final  stage  in  the  development  of  the  neurone, 
the  various  neurone  systems  would  naturally  become  myelinated  in  about  the  same  sequence 


502  TEXT-BOOK  OF  EMBRYOLOGY. 

in  which  their  axones  develop.  This  is  probably  true  in  a  general  way,  but  the  development 
of  both  axones  and  sheaths  requires  further  study  before  any  law  can  be  exactly  formulated. 
Coarse  fibers  apparently  become  medullated  early,  the  sheaths  of  such  fibers  being  usually 
thicker. 

Although  the  myelin  sheath  is  apparently  an  accessory  structure,  its  formation  is  of 
great  importance,  not  only  from  the  above  reason,  but  also  because  its  appearance  possibly 
indicates  the  assumption  by  the  neurone  of  its  capacity  for  the  precise  performance  of  its 
final  functions.  The  functional  significance  of  the  myelin  sheath  is  not,  however,  entirely 
clear.  Its  importance  is  enhanced  by  the  fact  that  its  integrity  depends  upon  the  integrity 
of  its  neurone  and  that  we  possess  precise  stains  for  demonstrating  both  its  normal  and 
abnormal  conditions. 

In  the  region  of  the  RHOMBENCEPHALON,  the  neural  crest  very  early  exhibits 
a  division  into  three  masses:  a  glossopharyngeo-vago-accessorius,  an  acustico- 
facialis,  and  a  trigeminus.  These  masses  soon  become  separated  from  each 
other  and  from  the  neural  tube,  the  glossopharyngeus  also  showing  a  partial 
separation  from  the  vago-accessorius  mass  (Fig.  434). 

The  vago-accessorius  group,  at  about  three  weeks,  is  a  mass  of  cells  much 
larger  at  the  cranial  end  and  continuous  by  a  narrow  band  of  irregular  cells 
with  the  spinal  neural  crest.  The  cranial  end  of  the  mass  shows  a  partial 
division  into  a  dorsal  and  ventral  part.  The  former  becomes  the  ganglion  of 
the  "vagus  root,  the  latter  the  ganglion  of  the  trunk  (nodosuiri).  The  glosso- 
pharyngeus mass  likewise  shows  a  division  into  a  dorsal  group  of  cells,  the 
future  ganglion  of  the  root  and  a  ventral  group,  the  future  ganglion  of  the 
trunk  (petrosum).  The  two  ventral  groups  are  associated  with  epidermal 
thickenings  (placodes),  but  it  is  doubtful  whether  any  ganglion  cells  are 
derived  from  the  thickenings.  These  thickenings  probably  represent  the 
thickenings  associated  in  water-inhabiting  Vertebrates  with  the  development  of 
certain  sense  organs,  either  lateral  line  or  epibranchial  (see  p.  459).  At  this 
stage  there  are  no  afferent  fibers,  the  cells  not  yet  being  differentiated  into 
neurones.  Some  fibers  found  among  the  cells  are  efferent  (see  p.  495).  The 
glossopharyngeus  cells  lie  in  the  region  of  the  third  branchial  arch,  the  vagus 
in  the  region  of  the  fourth. 

During  the  fourth  and  fifth  weeks  the  processes  of  the  cells  begin  to  develop 
(Fig.  434),  and  the  cell  masses  finally  become  definite  ganglia  with  afferent  root 
fibers  passing  into  the  neural  tube  and  peripheral  processes  passing  outward, 
forming,  with  the  associated  efferent  fibers,  the  peripheral  branches  of  the  nerves 
in  question  (Fig.  435).  The  root  and  trunk  ganglia  of  the  vagus  and  glosso- 
pharyngeus, respectively,  are  also  now  connected  by  fiber  bundles  instead  of 
cellular  strands.  At  the  same  time  there  is  a  diminution  of  cells  in  the  caudal 
part  of  the  vago-accessorius  group,  this  part  finally  being  composed  almost  ex- 
clusively of  efferent  fibers  emerging  from  the  lateral  surface  of  the  medulla  and 
cord.  A  few  groups  of  cells  (accessory  root  ganglia)  persist,  however,  and  develop 


THE  NERVOUS   SYSTEM. 


503 


into  ganglion  cells,  some  being  found  there  at  birth  (Streeter).  This  would  in- 
dicate the  presence  of  a  small  and  hitherto  undetected  afferent  element  in  the 
spinal  accessory  nerve,  which  is  usually  regarded  as  purely  efferent.  The  spinal 
accessory  nerves  are  thus  identical  with  the  vagus  in  their  early  development 
and  consist  at  first  of  a  homologous  series  of  efferent  roots  and  ganglia.  This 


Optha/  div 
Sup  max. 
N.  matticatorius 
Inf.  max.. 


ix-x-yi  gang,  crest. 


FIG.  434. — From  a  reconstruction  of  the  peripheral  nerves  in  a  human  embryo  of 

4  weeks  (6.9  mm.).     Streeter. 

III-XII,  III  to  XII  cranial  nerves;  C.I,  D.I..,  L.I.,  S.I.,  ist  cervical,  ist  dorsal,  ist  lumbar,  and 
ist  sacral  nerves,  respectively;  i,  2,  3.  branchial  arches;  Ot.  v.,  auditory  vesicle;  IX-X-XI 
gang,  crest,  ganglionic  or  neural  crest  of  IX,  X  and  XI  cranial  nerves.  Fiber  masses  are 
represented  by  fine  lines,  ganglion  cell  masses  by  dots. 

indicates  that  the  spinal  accessory  might  be  regarded  as  a  specialized  part 
of  the  vagus  extending  caudally  into  the  cord  (Streeter)  (see  p.  471).* 

From  this  point  on,  the  further  development  of  the  efferent  fibers  of  the  X 
and  XI  nerves  and  of  the  peripheral  processes  of  their  ganglia  is  the  further 

*  According  to  another  view  (Bremer),  the  spinal  accessory  nuclei  and  roots  are  to  be  regarded  as 
representing  a  specialization  of  lateral  nuclei  of  the  ventral  gray  column  of  the  cord  whose  root  fibers 
pass  in  the  dorsal  branches  of  the  spinal  nerves  to  the  dorsal  trunk  musculature  (p.  494,  comp.  Fig. 
404).  According  to  this  view,  the  muscles  innervated  by  the  XI  would  be  somatic.  The  possible 
homology  of  the  lateral  efferent  nuclei  and  roots  of  the  medulla  with  those  dorsal  root  fibers  of  the 
cord  which  arise  from  cells  in  the  ventral  gray  column  (p.  494  and  Fig.  430)  may  be  mentioned  in 
this  connection. 


504 


TEXT-BOOK  OF  EMBRYOLOGY. 


growth  of  the  various  branches  of  these  nerves  and  their  connection  with  the 
differentiating  structures  innervated  by  them.  At  the  same  time  there  is  an  in- 
creasing concentration  of  the  cells,  thereby  forming  more  definite  ganglionic 


Gang,  acusticum 

Gang,  semilunare  n  V 

Cerebellum         '     N.VI.    I 


Vesicula  auditiva 

Ga  g.  radicis  n.IX 


Gang,  petrosum 

Gang  radicis  n.X 


N.IIT" 

N.1V 


N.  frontal;*"" 


N  nasociliaris-'* 


N.  mandibularis 
Gang,  geniculatum 
N.  chorda  tympani 


Diaphragma'' 
Hepar .---'' 

I  Co. 


N.  tibialis-'" 
N.  peroneus" 

Tubus  digest. 


/Gang.  Froriep 


N.  hypoglossus 


L"=— JJ.XI. 

Gang,  rodos. 


»T         1 

N.  desc.  cerv. 
"Rami  hyoid. 
(Ansa  hypoglossi] 

N.  musculocutan, 
-jN.  axillaris 

N.  phrenicus 
— N.  medianus 

N.  radialis 
N.  ulnaris 

-ITh. 


R.  posterio 


N.  femoralis 
N.  obturatoriua 


R.  terminalis  lateralis 
R.  terminalis  anterior 
Mesonephros 


Nn.  ilioing.  et  hypogastr. 


FIG.  435. — Lateral  view  of  a  reconstruction  of  a  10  mm.  human  embryo,  showing  the  origin  and 
distribution  of  the  peripheral  nerves.  The  ganglionic  masses  are  represented  by  darker  and 
the  fiber  bundles  by  lighter  shading.  For  purposes  of  orientation  the  diaphragm  and  some 
of  the  viscera  are  shown.  The  arm  and  leg  are  represented  by  transparent  masses  into  the 
substance  of  which  the  nerve  branches  may  be  followed.  Streeter. 


THE   NERVOUS   SYSTEM. 


505 


masses.  The  changes  taking  place  are  similar  to  those  exhibited  in  the 
differentiation  of  the  spinal  nerves  (p.  497).  The  central  relations  of  the 
nerves  of  this  region  of  the  medulla  are  shown  in  Fig.  436.  (Comp.  Fig.  407). 
The  glossopharyngeus  at  the  same  time  develops  its  branches,  most  of  the 
peripheral  fibers  running  in  the  third  arch  (lingual  branch}.  Somewhat  later 
(12  to  14  mm.  embryo)  another  bundle  (tympanic  branch]  (Fig.  435)  passes  for- 
ward to  the  second  arch.  This  forms  the  typical  branchiomeric  arrangement 
in  which  there  is  a  forking  of  the  nerve  into  prebranchial  and  postbranchial 
branches,  the  latter  being  larger  and  containing  the  efferent  element  (see  p.  471 
and  Fig.  405). 


Roof  plate 

~    Alar  plate 

-    Fourth  ventricle 


Tractus  solitarius 

(in  marginal  layer) 


Efferent  nu.  N.  X. 
Nucleus  N.  XII.    - 

Ganglion  N.  X.     _  ^ 


"     Sulcus  limitans 


Inner  layer 


Mantle  layer 


of  basal 
plate 


~  Ventro-lat.  column 
(in  marginal  layer) 

—  Floor  plate 


FIG.  436. — Transverse  section  through  the  rhombic  brain  of  a  10.2  mm.  human  embryo  (during  the 
fifth  week).     X,  Vagus;  XII,  Hypoglossus.     His. 

While  the  ganglia  of  the  facialis  and  acusticus  are  derived  from  the  same 
mass  of  cells  (p.  502,  Fig.  434)  and  are  later  still  in  very  close  apposition,  it  must 
be  remembered  that  they  are  totally  different  in  character.  At  four  weeks  they 
are  differentiated  from  each  other  (Fig.  437).  The  relations  of  the  two  ganglia 
are  shown  in  Figs.  435  and  437.  It  is  probable  that  the  ganglion  of  the  facial 
(geniculate  ganglion)  shows  an  early  differentiation  into  dorsal  and  ventral 
parts  similar  to  the  ganglia  of  the  IX,  and  X,  and  also  has  associated  placodes. 
The  peripheral  branches  of  the  cells  of  the  geniculate  ganglion  develop  into  the 
great  superficial  petrosal  and  chorda  tympani.  Both  of  these  nerves  enter  into 
secondary  relations  with  the  V.  There  is  some  doubt  as  to  whether  the  chorda 
is  a  prebranchial  or  postbranchial  nerve  (Fig.  435;  also  compare  p.  469  and 
Figs.  405  and  406). 


506 


TEXT-BOOK  OF  EMBRYOLOGY. 


The  VII,  IX  and  X  are,  as  already  mentioned,  branchial  (splanchnic) 
nerves  and  the  central  processes  of  their  ganglia  all  have  a  common  destina- 
tion; they  grow  into  the  lateral  surface  of  the  medulla  oblongata,  enter  the 
marginal  layer  of  the  alar  plate,  and  there  bend  caudally,  forming  a  common 
descending  bundle  of  fibers  in  the  marginal  layer,  the  tractus  solitarius 
(Figs.  436  and  470;  see  also  pp.  469,  472). 

The  acoustic  ganglionic  mass  is  elongated  at  an  early  stage,  and  is  in  con- 
nection with  an  ectodermal  thickening  (placode)  which  gives  rise  to  the  acoustic 


m.G.v. 


Roof  plate 


Alar  plate 

Sulcus  limitans 

Basal  plate 


Floor  plate 


FIG.  437. — Transverse  section  through  the  acoustic  region  of  the  rhombic  brain  of  a  10.2  mm.  human 
embryo.  VI,  Abducens  and  its  nucleus;  VII  G.  g.,  geniculate  ganglion;  VIII G.  c.,  cochlear 
ganglion  of  acoustic  nerve;  VIIIG.v.,  vestibular  ganglion  of  VIII  nerve.  His. 

receptors  (p.  598).  From  the  upper  part  of  the  mass  a  bundle  of  peripheral 
processes  forms  a  branch  which  subsequently  innervates  the  ampullae  of  the 
superior  and  lateral  semicircular  canals  and  the  utricle,  while  from  the  lower 
part  a  branch  develops  to  the  ampulla  of  the  posterior  canal  and  to  the  saccule. 
The  nerve  and  ganglion  (ganglion  of  Scarpa)  is  thus  at  first  vestibular  and  at 
this  stage  the  cochlear  part  of  the  ear  vesicle  is  not  indicated  as  a  separate  out- 
growth. As  the  lower  border  of  the  vesicle  grows  out  into  the  cochlea,  the 
lower  border  of  the  ganglion  becomes  thickened  and  develops  into  the  cochlear 
ganglion  (the  ganglion  spirale).  It  will  be  recalled  that  the  vestibular  part  o£ 


THE  NERVOUS   SYSTEM. 


507 


the  ear  is  the  older  part  phylogenetically,  the  cochlea  being  a  more  recent  special- 
ized diverticulum  of  the  older  structure.    (See  p.  599  and  Figs.  512  and  513.) 

The  central  processes  of  the  acoustic  ganglionic  mass  first  develop  from  the 
upper  part,  forming  the  vestibular  nerve  root  which  enters  the  marginal  layer  of 
the  medulla.  A  portion  at  least  of  its  fibers  bends  caudally,  forming  a  de- 
scending tract.  The  central  processes  of  the  cells  of  the  cochlear  ganglion, 
forming  the  cochlear  nerve  root,  pass  dorsally,  cross  the  vestibular  ganglion  and 
enter  the  medulla  dorsal  and  lateral  to  the  vestibular  root  fibers  (Fig.  437). 

Roof  plate 


FIG.  438. — Transverse  section  through  the  rhombic  brain  in  the  region  of  the  trigeminus  (V)  nerve 
of  a  10.2  mm.  human  embryo.  a.W.,  Spinal  V;  G.G.,  Gasserian  ganglion;  V. m.,  efferent 
root  of  V  nerve.  His. 

The  trigeminus  is  the  most  anterior  of  the  ganglionic  masses  (Fig.  434). 
Embryological  evidence  has  been  brought  to  show  that  it  consists  of  two  or 
more  nerves  which  subsequently  fuse.  Placodes  have  also  been  described. 
It  is  possible  that  such  placodes  represent  those  belonging  to  the  most  anterior 
division  of  the  lateral  line  system  in  lower  forms,  and  probably  in  this  case 
would  not  properly  belong  to  the  V  (comp.  Fig.  405).  From  the  ganglionic 
mass  (Gasserian  or  semilunar  ganglion)  the  three  principal  branches — oph- 
thalmic, maxillary  and  mandibular — are  formed,  the  two  latter  passing  into  the 


508 


TEXT-BOOK  OF  EMBRYOLOGY. 


Roof  plate 


Alar 
plate. 


FIG.  439. — Transverse  section  through  the  trigeminal  region  of  the  rhombic  brain  of  a  10.2  mm. 
human  embryo,  a.  W.,  Spinal  V;  V.  s.,  Gasserian  ganglion;  V.  m.,  part  of  efferent  root  of 
V  nerve.  His. 


FIG.  440.     Part  of  a  transverse  section  through  the  rhombic  brain  of  a  chick  embryo  toward  the 

fourth  day,  showing  the  trigeminal  roots.     Cajal. 
A,  part  of  the  efferent  (masticator)  nucleus  of  the  V;  B,  efferent  root  of  the  V;  C,  bipolar  cells  of 

the  Gasserian  ganglion;  D,  beginning  of  descending  tract  (spinal  V)  formed  by  the  central 

processes  of  C. 


THE  NERVOUS  SYSTEM.  509 

maxillary  process  and  mandibular  arch,  respectively  (Fig.  435).  The  central 
processes,  forming  the  afferent  root  (portio  major}  of  the  V,  enter  the  marginal 
layer  of  the  alar  plate  of  the  rhombencephalon  and  form  a  descending  bundle, 
the  spinal  V  (Figs.  438,  439,  440  and  470). 

The  trigeminus  exhibits  its  spinal-like  character  in  the  behavior  of  its 
visceral  portion  (comp.  p.  498).  Cells  of  the  ganglionic  mass  migrate  further 
peripherally  and  form  sympathetic  ganglia  (ciliary,  otic,  sphenopalatine  (?} 
submaxillary(?)  ).  As  in  the  cord,  the  question  has  arisen  whether  efferent 
roots  may  not  also  contribute  a  portion.  Cells  have  been  described  as  migrat- 
ing with  the  oculomotor  root  fibers  and  forming  part  of  the  ciliary  ganglion 
(Carpenter). 

Besides  those  already  described  (cerebrospinal,  sympathetic),  the  only 
other  peripheral  neurones  of  the  nervous  system  are  connected  with  the  PROS- 
ENCEPHALON  and  are  a  part  of  the  eye  and  nose.  The  visual  receptors  (rods 
and  cones)  and  peripheral  afferent  neurones  (bipolar  cells)  appear  to  be  repre- 
sented by  portions  of  the  retina  and  are  described  elsewhere  (Chap.  XVIII). 

In  the  nose  there  is  first  a  placode  (p.  459)  from  which  neuroblasts  develop. 
Some  of  these  migrate  toward  the  neural  tube  and  probably  differentiate  into 
lemmocytes,  a  few  becoming  ganglion  cells.*  The  majority  of  the  neuroblasts 
remain  in  the  olfactory  epithelium,  sending  their  axones  (fila  olfactorid)  into 
the  olfactory  bulb,  the  peripheral  afferent  olfactory  neurones  thus  apparently 
displaying  the  primitive  ectodermal  location  of  afferent  peripheral  neurones 
(p.  455  and  Fig.  397).  (Comp.  p.  591.) 

Development  of  the  Lower  (Intersegmental)  Intermediate  Neurones. 

It  has  already  been  seen  how,  by  migration  and  by  differentiation  of  the  cells 
during  migration,  the  nucleated  layer  comprising  the  greater  part  of  the  thick- 
ness of  the  wall  of  the  neural  tube  is  differentiated  into  two  layers — an  inner 
nucleated  layer  retaining  its  earlier  characteristics,  and  an  outer  nucleated 
(mantle)  layer,  composed  largely  of  the  differentiating  neuroblasts  and 
characterized  in  ordinary  staining  by  more  widely  separated  nuclei.  It  has 
also  been  seen  that  this  differentiation  takes  place  earlier  and  more  rapidly  at 
first  in  the  ventral  part  of  the  lateral  walls  (basal  plate) ,  and  that  the  first  cells  to 
migrate  and  differentiate  are  those  whose  axones  grow  out  through  the  neural 
wall  and  pass  out  as  the  ventral  root  fibers. 

Not  much  later  than  the  above  differentiation  of  the  efferent  peripheral 
neurones,  axones  of  other  neuroblasts  also  grow  toward  the  periphery  of  the 
tube  but  do  not  pass  beyond  its  wall.  Such  neuroblasts  become  intermediate 

*  The  latter  are  probably  transient,  but  possibly  in  some  forms  persist  as  the  ganglion  cells  of  the 
nervus  terminalis  of  Pinkus. 


510 


TEXT-BOOK:  OF  EMBRYOLOGY. 


neurones  (p.  456).  The  migrating  bodies  of  these  neuroblasts  are  checked  at 
the  inner  boundary  of  the  marginal  layer,  but  their  growing  axones  enter  the 
marginal  layer  and  there,  apparently  on  account  of  their  inability  to  penetrate 
the  external  limiting  membrane,  turn  cranially  or  caudally,  or  bifurcate,  and 
form  longitudinal  ascending  and  descending  fibers.  These  longitudinal  fibers 
constitute  a  part  of  the  future  white  columns  (see  p.  514),  and  their  cells  are 
therefore  often  called  column  cells.  Many  axones  from  such  cells  in  all  parts 
of  the  lateral  walls  (heteromeric  or  commissural  column  cells)  pursue  a  ven- 
tral course  through  the  mantle  layer,  arching  around  near  the  periphery  and 


FIG.  441. — Part  of  a  section  through  the  lumbar  spinal  cord  of  a  76-hour  chick  embryo.     Cajal. 
A,  Ventral  root;  B,  spinal  ganglion;  C,  bifurcation  of  dorsal  root  fibers  forming  beginning  of  dorsal 
funiculus;  a,  b,  c,  neuroblasts  showing  various    stages  of  differentiation    into    intermediate 
neurones,  some,  at  least,  (c)  becoming  heteromeric  column  cells;  d,  efferent  neurone. 


crossing  the  floor  plate,  ventral  to  the  lumen,  to  become  longitudinal  ascending 
and  descending  fibers  in  the  marginal  zone  of  the  opposite  side.  These  early 
decussating  axones  form,  in  the  cord,  the  beginning  of  the  anterior  commissure 
(Fig.  441).  Other  neuroblasts,  the  axones  of  which  do  not  cross  the  median 
line,  become  tautomeric  column  cells. 

It  is  about  this  time  that  the  afferent  root  fibers  enter  the  marginal  layer  of 
the  dorsal  part  (alar  plate)  of  the  lateral  wall  and  form  in  the  marginal  layer 
the  various  bundles  of  longitudinal  fibers  above  described  (dorsal  funiculus, 
tractus  solitarius,  descending  vestibular,  and  spinal  V)  (Figs.  441,  442,  436,  437, 


THE  NERVOUS   SYSTEM.  511 

439,  440  and  470).  In  the  cord  the  ascending  arms  grow  to  a  greater  length 
than  the  descending.  In  the  rhombic  brain  the  reverse  is  usually  the  case. 

The  longitudinal  fibers  of  the  afferent  roots  and  of  the  intermediate  neurones 
thus  form  an  external  layer  occupying  the  marginal  layer  of  the  neural  tube. 
This  is  the  beginning  of  the  differentiation  into  white  and  gray  matter,  i.e., 
into  that  part  of  the  neural  tube  containing  only  the  axones  of  the  neurones 
and  into  that  part  containing  the  cell  bodies  and  the  beginnings  and  termina- 
tions of  the  axones.  The  terminations  of  axones  are  formed  by  a  turning  of 
the  longitudinal  fibers  into  the  mantle  layer  or  gray  matter  to  form  there 
terminal  arborizations.  Later,  the  longitudinal  fibers  develop  branches  (col- 
laterals) which  also  pass  into  the  gray  matter.  The  differentiation  of  the 
white  matter  is  completed  several  months  later  by  the  myelination  of  the 
nerve  fibers. 

The  longitudinal  axones  of  intermediate  neurones  which  are  formed  at  this 
period  in  the  cord  and  epichordal  brain  are  located  ventrally  near  the  median 
line.  These  medial  tracts  occupy  the  position -of  the  future  medial  longitu- 
dinal fasciculi,  the  reticulo-spinal  and  ventral  ground  bundles,  and  may  be 
regarded  on  both  comparative  anatomical  and  embryological  grounds  as  a 
primitive  system  of  long  and  short  ascending  and  descending  tracts  mediating 
between  cerebrospinal  afferent  and  efferent  peripheral  neurones,  and  not 
having  at  this  period  connections  with  the  higher  centers.  Other  more  lateral 
tracts  of  this  character  are  formed  somewhat  later,  the  whole  forming  the 
beginning  of  the  reticular  formation  +  ventro-lateral  ground  bundle  system 
(compare  Figs.  442,  449,  452  and  454). 

While  merging  more  or  less  imperceptibly  into  the  following  stages,  it  may 
in  a  general  way  be  said  that  at  this  stage  of  development  there  is  differentiated 
what  might  be  termed  the  primary  and  probably  the  oldest  coordinating  mech- 
anism of  the  nervous  system,  most  clearly  segmental  in  character  and  having 
general  features  common  not  only  to  all  Vertebrates,  but  to  many  Invertebrates. 
It  is  characterized  by  afferent  and  efferent  peripheral  neurones  arranged  seg- 
mentally  and  connected  longitudinally  in  the  central  nervous  system  by  crossed 
and  uncrossed  intersegmental  intermediate  neurones.  (Compare  pp.  472  and 
473) .  At  the  anterior  end  of  this  part  of  the  nervous  system  (epichordal  segmen- 
tal brain)  there  are  also  exhibited  differentiations  due  to  fundamental  vertebrate 
differentiations  in  the  peripheral  receptive  and  effective  apparatus.  Some  of 
these  are:  (i)  The  differentiation  of  the  splanchnic  (visceral)  receptive  and 
motor  apparatus,  giving  rise  in  the  nervous  system  to  (a)  a  separate  system  of 
afferent  root  fibers  (tractus  solitarius)  including  the  more  specialized  gustatory 
apparatus;  (b)  a  distinct  series  of  lateral  efferent  nuclei.  (2)  The  concentra- 
tion of  the  non-specialized  somatic  afferent  innervation  into  one  nerve  (tri- 

33 


512  TEXT-BOOK  OF  EMBRYOLOGY. 

* 
geminus   and  its  central  continuation,  the    spinal  V).      (3)  The  specialized 

somatic  sense  organ,  the  ear,  with  its  older  vestibular  and  newer  cochlear 
divisions  with  central  continuations  of  its  nerves,  including  a  vestibular 
descending  tract. 

These  differentiations  of  the  peripheral  afferent  apparatus  lead  to  the  later 
formation  of  special  terminal  nuclei  for  their  central  continuations  and  second- 
ary tracts  from  these  nuclei  to  suprasegmental  structures  (p.  473,  Fig.  409). 

The  peripheral  and  intermediate  neurones  of  the  more  highly  modified 
cranial  end  of  the  tube,  or  FORE-BRAIN,  appear  to  lag  behind  in  development, 
but  in  its  basal  part  the  neuroblasts  are  beginning  to  be  differentiated  (fifth 
week).  In  the  development  of  the  eye,  the  brain  wall  is  evaginated,  carrying 
with  it  the  future  retina  comprising,  apparently,  the  sensory  epithelial  cells  or 
receptors  (rods  and  cones),  the  afferent  peripheral  neurones  (bipolar  cells  of 
retina)  and  the  receptive  or  primary  intermediate  neurones  (ganglion  cells  of 
retina  and  optic  nerve).  The  histogenesis  of  these  elements  is  dealt  with 
elsewhere,  but  it  may  be  pointed  out  here  that  the  axones  of  the  ganglion 
cells  of  the  retina  grow  toward  the  inner  side  of  the  optic  cup  (away  from 
the  original  luminal  surface),  pass  thence  in  the  marginal  layer  of  the  optic 
stalk,  undergo  a  partial  ventral  decussation  (optic  chiasma)  in  the  floor  plate, 
and  terminate  in  certain  thalamic  nuclei  (lateral  geniculate  bodies)  and  in  the 
roof  of  the  mid-brain.  The  so-called  optic  nerve  is  thus  obviously  a  central, 
secondary  tract.  The  development  of  this  tract  does  not  apparently  take  place 
until  a  later  period  than  the  differentiation  of  the  earlier  secondary  tracts  of  the 
cord  and  rhombic  brain  (after  the  sixth  week) . 

In  the  case  of  the  olfactory  organ,  it  has  already  been  seen  that  the  peripheral 
neurones  develop  at  first  apart  from  the  neural  tube  and  send  their  axones 
into  the  olfactory  bulb.  The  latter  is  an  evagination  of  the  neural  tube 
which  receives  the  olfactory  fibers,  thereby  constituting  a  complicated  terminal 
nucleus  for  the  latter.  The  axones  of  bulb  cells  (the  mitral  cells]  which  pass 
along  the  stalk  of  the  bulb  are  thus  the  secondary  tract  of  this  system.  Many 
of  them  decussate  in  the  anterior  commissure.  Secondary  (and  tertiary) 
olfactory  tracts  find  their  way  to  caudal  parts  of  the  rhinencephalon  and  to 
hypothalamus,  thalamus  and  epithalamus,  forming,  with  other  tracts,  a  highly 
modified  prechordal  intersegmental  mechanism  (p.  544).  Other  olfactory  tracts 
proceed  to  the  suprasegmental  archipallium  which  develops  efferent  bundles 
to  the  segmental  brain. 

The  embryological  development  of  the  peripheral  apparatus,  especially 
of  its  receptive  portions,  as  shown  by  the  various  separate  ganglionic  rudiments 
(Fig.  434)  and  placodes,  exhibits  a  segmental  character  which,  though  not 
in  all  respects  primitive,  is  of  practical  value.  These  segments  are  (Adolf 
Meyer):  (i)  The  olfactory  apparatus,  nose,  without  efferent  elements.  (2) 


THE  NERVOUS   SYSTEM.  513 

The  visual  apparatus,  eye,  with  the  eye-moving  III  and  IV  mid-brain  nerves 
as  its  efferent  portion.  (3)  The  general  sensory  apparatus  of  the  surfaces  of 
the  head  and  mouth,  the  afferent  trigeminus,  with  the  jaw-moving  efferent 
trigeminus.  (4)  The  auditory  (and  vestibular)  apparatus,  the  ear  (VIII 
nerve),  with  the  VI  (turning  the  eye  to  the  source  of  sound)  and  VII  (ear  and 
face  muscles)  efferent  nerves.  In  the  latter,  the  original  ear-moving  apparatus 
has  been  replaced  largely,  in  man,  by  the  muscles  of  expression.  "  (5)  The 
•visceral  segment  (IX,  X,  and  XII  nerves) ,  not  indicated  externally  in  forms  with- 
out gills.  The  afferent  portion  is  concerned  with  taste  and  visceral  stimuli, 
the  efferent  with  tasting,  swallowing,  sound-production  and  other  visceral 
functions.  Overlapping  with  other  segments  is  due  to  its  visceral  as  opposed 
their  somatic  chracter.  The  apparent  dislocation  shown  by  the  abducens  is 
due  to  its  common  use  by  more  than  one  segment. 

Caudal  to  this  is  the  mechanism  for  head  movement  (N.  XI),  its  afferent  por- 
tion being  the  upper  spinal  nerves.  Following  this,  there  is  the  segmental 
series  of  spinal  nerves  which  in  places  shows  a  tendency  to  fuse  (plexuses)  into 
larger  segments  (phrenic  segment,  limb  segments).  All  such  modifications  are 
expressions  of  more  recent  functional  adjustments  modifying  preexisting  ones. 

These  segments  may  be  regarded  as  a  series  of  reflex  arcs,  each  one  of 
which  may  have  a  certain  amount  of  physiological  independence  but  which 
are  associated  by  intersegmental  neurones.  The  latter  class  of  intermediate 
neurones  probably  effects  certain  groupings  of  various  efferent  neurones,  fur- 
nishing mechanisms  which  secure  harmonious  responses  of  groups  of  effectors 
involved  in  certain  definite  reactions  (e.g.,  limb-movements,  associated  eye 
movements).  These  effector-associating  mechanisms  may  be  acted  on  di- 
rectly (reflex)  by  afferent  neurones  or  by  the  efferent  arms  of  suprasegmental 
mechanisms. 

Superadded  to  this  segmental  apparatus  are  the  suprasegmental  mechanisms 
which  develop  later,  the  pallium  being  the  last  to  be  completed.  These  re- 
ceive bundles  from  the  segmental  nervous  system  and  send  descending  bundles 
to  the  intersegmental  neurones  (pp.  464,  472  and  473  and  Fig.  409). 

FURTHER  DIFFERENTIATION  OF  THE  NEURAL  TUBE. 
The  Spinal  Cord. 

From  this  time  on,  differences  of  structure  between  cord  and  epichordal 
segmental  brain  become  more  marked  and  make  it  more  convenient  to  treat 
their  later  development  separately.  The  ventral  half  of  the  cord  for  a  con- 
siderable period  maintains  its  lead  in  development.  At  four  weeks  (Fig.  442) 
this  lead  is  not  so  pronounced  as  in  the  immediately  following  period.  At 
this  stage  it  will  be  noticed  that  the  lumen  is  narrower  in  the  ventral  part, 


514 


TEXT-BOOK  OF  EMBRYOLOGY. 


as  if  due  to  the  greater  thickening  of  the  ventral  walls  (basal  plates).  The 
increase  of  the  mantle  layer  (gray)  of  the  basal  plate  marks  the  beginning  of 
the  ventral  (anterior}  gray  column  or  horn.  The  increase  in  the  basal  plate 
may  be  partly  due  to  neuroblasts  migrating  from  the  alar  plate.  These 
would  be  intermediate  neurones.  The  development  of  the  mantle  layer  at 
the  expense  of  the  inner  layer,  due  to  differentiation  and  migration  of  the  cells 
of  the  lafter,  is  well  shown,  but  is  more  marked  in  the  following  stages. 

As  already  mentioned,  the  axones  of  the  heteromeric  cells,  many  of  which 
lie  in  the  dorsal  half  of  the  lateral  walls,  after  decussating  (anterior  commis- 


Beginning  of       /.• 
dorsal  funiculus  VA  ' 


Dorsal  root  2^ 
Mantle  layer* 


Meningeal 
membrane 


Ventral  root 
(from  neuroblasts*-fgj 
of  mantle  layer) 


FIG.  442. — Half  of  a  transverse  section  of  the  spinal  cord  of  a  4  weeks,  (6.9  mm.)  human  embryo. 
Dp,  Roof  plate;  Bp,  floor  plate.     His. 

sure),  form  longitudinal  fibers  in  the  marginal  layer  along  the  ventral  surface 
of  the  opposite  side,  mostly  mesial  to  the  emerging  ventral  roots  (Fig.  442). 
These  longitudinal  fibers  are  the  beginning  of  the  ventral  (anterior)  white  columns 
or  funiculi  of  the  cord.  The  sides  of  the  tube  between  the  dorsal  and  ventral 
roots  contain  at  first  only  a  few  longitudinal  fibers — the  beginning  of  the  ventro- 
lateral  funiculi.  Their  number  soon  rapidly  increases,  the  fibers  apparently 
coming  from  ventrally  located  tautomeric  cells.  The  dorsal  root  fibers,  as 
stated  before  (p.  497),  form  small  round  bundles  in  the  marginal  layer  of  the 
dorsal  halves  (Fig.  442).  This  is  the  beginning  of  the  dorsal  (posterior)  white 
columns  or  funiculi. 


THE  NERVOUS   SYSTEM. 


515 


At  four  weeks  there  are  blood  vessels  in  the  mesodermal  tissue  surrounding 
the  neural  tube.  Branches  of  these  soon  penetrate  the  tube  itself. 

From  its  first  appearance  in  the  cord  as  an  oval  bundle,  during  the  fourth 
week,  the  dorsal  funiculus  steadily  increases  in  size,  forming  a  "root  zone"  in 
the  marginal  layer  of  the  dorsal  half,  but  not  reaching  the  roof  plate  (Fig.  443). 
This  increase  in  size  is  probably  produced  in  part  by  the  addition  on  its 
inner  side  of  overlapping  ascending  arms  of  dorsal  root  fibers  from  lower 


Partly  differentiated  mantle  layer 
Mantle  layer 


Dorsal  funiculus 
(post,  white  column)    * 


Lateral  gray 
column  (lat.  horn) 


Ventral  root 


FIG.  443. — Half  of  a  transverse  section  of  the  spinal  cord  of  a  4^  weeks  (10.9  mm.)  human  embryo.  His. 
A.s.,  Artery  in  ventral  longitudinal  sulcus;  A.sp.  a.,  ventral  (anterior)  spinal  artery;  Bp,  floor  plate; 
Dp,  roof  plate;  1. 1.,  inner  layer.     The  faint  inner  outline  is  the  outline  of  the  cord  proper. 

cord  segments.  The  mantle  layer  of  this  part  contains  an  increasing  number 
of  cells  forming  curved  or  arcuate  fibers.  (Fig.  443.)  The  increase  in  the 
mantle  cells  of  the  dorsal  part  marks  the  beginning  of  the  dorsal  (posterior) 
gray  column  or  horn  (terminal  nucleus  of  the  dorsal  root  fibers).  Later,  other 
cells  become  differentiated  from  the  inner  layer  which  do  not  apparently  form 
arcuate  fibers  (Fig.  443)  and  which  subsequently  become  part  of  the  posterior 
horn.  It  is  possible  that  the  axones  of  some  of  these  cells  form  the  compara- 


516 


TEXT-BOOK  OF  EMBRYOLOGY. 


tively  small  ground  bundles  of  the  dorsal  funiculus.  During  this  period 
of  development  of  the  dorsal  portions  of  the  lateral  walls  the  latter  have  ap- 
proached each  other,  reducing  the  dorsal  part  of  the  lumen  to  a  slit.  The 
roof  plate  has  undergone  a  slight  infolding  (Fig.  444).  Ventral  to  the  dorsal 
roots  there  is  a  groove  running  along  each  side  of  the  cord  (marginal  furrow  of 
His).  At  four  and  one-half  weeks  the  number  of  fibers  of  the  ventro-lateral 
funiculus  has  greatly  increased  and  another  groove  has  appeared  parallel  and 
ventral  to  the  marginal  furrow  and  forming  the  dorsal  boundary  of  the  ventro- 

Y 


Dors,  funiculus 

Dors,  gray  column  (post,  horn) 

Dors,  root 
Marginal  furrow 
Cylinder  furrow 


Intermediate  plate 
Central  canal  - 


Floor  plate  -  - 


Vent.  long,  sulcus    


-  Lat.  gray  column  (lat.  horn) 

-  Ventro-lat.  funiculus 

.  Vent,  gray  column  (ant.  horn) 

-  Vent,  root 


Vent,  funiculus 
(ant.  white  column) 


Vent.  sp.  artery 

FIG.  444. — Half  of  a  transverse  section  of  the  spinal  cord  of  a  human  embryo 
of  18.5  mm.  (7^  weeks).     His. 

lateral  funiculus  (cylinder  furrow  of  His)  (Figs.  443  and  444).  The  portion 
of  the  lateral  wall  lying  between  these  two  grooves  or  furrows  forms  an 
intermediate  plate  which  contains  few  fibers  in  its  marginal  layer  at  this 
period,  and  is  thus  backward  in  development.  Grooves  appear  on  the  luminal 
wall,  apparently  corresponding  approximately  to  the  outer  grooves. 

The  further  growth  of  the  dorsal  funiculi  and  the  concomitant  growth 
of  the  associated  gray  matter,  i.e.,  of  the  cells  of  the  adjoining  mantle  layer, 
proceed  until  we  have  the  conditions  shown  in  Figs.  444  and  445.  At  the 
same  time  there  is  a  further  approximation  of  the  dorsal  portions  of  the  lateral 


THE  NERVOUS   SYSTEM 


517 


walls  so  that  the  widest  part  of  the  lumen  is  further  ventral.  At  about  eight 
weeks  the  portion  of  the  wall  near  the  median  line,  which  has  formed  a  ridge 
by  the  apposition  of  the  two  inner  layers  and  the  roof  plate  (Fig.  444  Y) ,  and  is 
uncovered  as  yet  with  fibers,  differentiates  a  marginal  layer  (eight  and  one-half 
weeks,  Fig.  445)  into  which  fibers  grow  forming,  on  each  side,  in  the  upper 
part  of  the  cord,  the  column  of  Goll  or  fasciculus  gracilis  (Fig.  446) .  Many 
of  these  fibers,  at  least,  are  the  ascending  arms  of  caudal  dorsal  root  fibers, 
which  are  thus  added  mesially  to  the  continuations  of  upper  cord  roots.  It  will 


Rudiment  of  funiculus  gracilis 


Dorsal  funiculus  (cuneatus) 


Intermediate  plate  -  - 


Central  canal   - 


Floor  plate  -  - 


Vent.  long,  sulcus  —  -  - 


Dors,  gray  column 
-  ---  Dors,  root 

N 

L.  .\. . .  Marginal  furrow 
- J  Cylinder  furrow 

-  Lat.  gray  column 

-•  Ventro-lat.  funiculus 

Vent,  gray  column 

Vent,  root 

-  Vent,  funiculus 


Vent.  sp.  art. 

FIG.  445. — Half  of  a  transverse  section  of  the  spinal  cord  of  a  human  embryo  of 
24  mm.  (8£  weeks).     His. 

be  noted  that  there  is  now  a  massive  dorsal  gray  column  and  that  the  original 
oval  bundle  has  extended  around  on  the  mesial  side  of  this  gray  column. 

While  these  changes  are  taking  place,  the  dorsal  portions  of  the  lateral  walls 
have  fused,  probably  beginning  at  the  most  dorsal  part,  thus  forming  the  dorsal 
septum.  This  may  be  accompanied  by  a  certain  amount  of  rolling  in  from  the 
dorsal  part  indicated  by  the  direction  of  the  ependyma  cells  (Fig.  445).  The 
growth  of  the  ventral  funiculi  and  gray  columns  results  in  the  appearance 
and  subsequent  increasing  depth  of  the  ventral  longitudinal  fissure.  The  cord 
now  resembles  the  adult  cord  in  many  features,  having  well-marked  white*  and 

*The  term  "white  "  column  is  used  for  convenience.  The  funiculi  do  not  become  "white"  until 
their  fibers  become  myelinated  during  the  sixth  month. 


518 


TEXT-BOOK  OF  EMBRYOLOGY. 


gray  columns,  but  contains  a  disproportionately  small  amount  of  fibers.  A 
further  and  later  change  consists  in  a  rolling  inward,  as  it  were,  of  the  dorsal 
gray  column  so  that  it  becomes  separated  from  the  ventral  gray  column,  and 
that  portion  of  it  formerly  facing  dorsally  comes  to  face  more  mesially,  the  roots 
entering  more  dorsally.  This  change  may  be  due  partly  to  the  development 
of  the  intermediate  plate  which  has  in  the  meantime  taken  place.  In  this 
plate  axones  of  tautomeric  cells  have  begun  to  form  the  limiting  layer  of  the 
lateral  funiculus.  From  the  cells  of  the  intermediate  plate  are  formed  the 
neck  of  the  dorsal  gray  column,  also  the  cells  of  Clarke's  column  and  the 

Funiculus  gracilis 


Dors,  funiculus  (cuneatus) 
Dors,  gray  column 
Dors,  root 

Marginal  furrow 
Intermed.  plate 
Cylinder  furrow 


\~  ~  —  Lat.  gray  column 


Ventro-lat.  funiculus 
Vent,  gray  column 

Vent,  root 


Vent.  long,  sulcus 


Vent,  funiculus 
Vent.  sp.  artery 
FIG.  446. — Half  of  a  transverse  section  of  the  spinal  cord  of  a  human  foetus  of  about  3  months.    His. 

processus  reticularis.  In  the  course  of  these  developments,  the  ventro-lateral 
ground  bundles,  formed  primarily  by  heteromeric  and  tautomeric  cord  cells, 
receives  various  accessions.  These  are  first  the  long  descending  inter- 
segmental  tracts  from  epichordal  brain  nuclei  in  the  formatio  reticularis 
which  as  they  proceed  down  the  cord  naturally  overlap  externally  the  ground 
bundles  already  formed  there.  They  include  the  medial  longitudinal  fasciculi, 
tracts  from  Deiters1  nuclei  and  the  rubro-spinal  tracts  which  occupy  the  ventro- 
lateral  funiculi  external  to  the  ground  bundles.  In  the  lateral  funiculi  there 
are  also  added  the  ascending  tracts  from  cord  nuclei  to  suprasegmental  structures. 


THE  NERVOUS   SYSTEM.  519 

These  are  the  dorsal  spino-cerebellar  tracts  from  Clarke's  columns,  ventral  spino- 
cerebellar  tracts,  and  tracts  to  mid-brain  roof  and  thalamus  (spino-tectal  and 
ihalamic].  Finally  (fifth  month)  the  descending  tracts  from  the  pallium  are 
added,  the  direct  and  crossed  cor tico- spinal  (pallia- spinal  or  pyramidal)  tracts, 
the  latter  being  thrust,  as  it  were,  into  the  lateral  funiculus. 

The  development  of  the  cord,  then,  is  produced  by  (i)  the  proliferation  of 
the  epithelial  cells  and  the  formation  of  the  nuclear  and  marginal  layers;  (2) 
the  multiplication,  differentiation  and  growth  of  the  neuroblasts  (mantle  layer) ; 
(3)  the  development  of  the  ventral  roots;  (4)  formation  of  the  funiculi  (white 
columns  when  myelinated)  by  the  growth  into  the  marginal  layer  of  (a)  dorsal 
root  fibers  of  the  cord,  the  ascending  arms  of  which  overlap  those  root  fibres 
entering  higher  cord  segments,  (b)  cord  neuroblasts  forming  intersegmental 
(ground  bundle)  tracts  next  to  the  gray  matter,  (c)  descending  intersegmental 
tracts  from  the  segmental  brain,  representing  continuations  principally  of  cere- 
bellar  efferent  tracts,  (d)  afferent  suprasegmental  tracts  from  cord  nuclei, 
(e)  descending  pallio-spinal  tracts.  In  addition  to  this,  there  are  general 
factors  of  growth,  such  as  increasing  vascularization,  increasing  amount  of 
neurone  cytoplasm  (especially  dendrites) ,  increased  size  of  axones  and,  finally, 
the  acquisition  by  the  latter  of  myelin  sheaths. 

The  vertebral  column  grows  faster  in  length  than  the  inclosed  spinal  cord. 
The  result  of  this  is  that  the  caudal  spinal  nerves  making  their  exit  through  the 
intervertebral  foramina  are,  so  to  speak,  dragged  caudalward  and  instead  of 
proceeding  outward  at  right  angle  to  the  cord,  pass  caudally  to  reach  their 
foramina.  The  leash  of  nerve  roots  thus  formed,  lying  within  the  caudal  part 
of  the  vertebral  column,  constitutes  the  cauda  equina.  The  coverings  of  the 
cord  retain  their  original  connections  at  the  caudal  end  of  the  vertebral  canal 
and  form  a  prolongation  of  the  cord  membranes  enclosing  the  thin,  terminal 
part  of  the  cord,  ihefilum  terminate. 

The  Epichordal  Segmental  Brain. 

In  the  fifth  week,  the  walls  of  the  rhombencephalon  are  comparatively  thin. 
In  the  caudal  region  of  the  medulla  oblongata  (p.  484),  the  dorsal  part  of  each 
lateral  wall  is  upright  and  is  bent  at  a  considerable  angle  with  the  ventral 
part  (basal  plate),  the  groove  on  the  inner  surface  between  the  two  being  the 
sulcus  limitans.  The  roof  of  this  region  is  formed  by  the  thin  expanded  roof 
plate  (Figs.  436-439). 

Anterior  to  this,  the  roof  plate  is  not  expanded,  the  alar  plates  almost 
meeting  in  the  mid-dorsal  line.  This  thicker  part  of  the  roof  is  the  rudiment 
of  the  cerebellum.  Its  caudal  edges  are  attached  to  the  expanded  roof  plate  (see 
P-  532). 


520 


TEXT-BOOK  OF  EMBRYOLOGY. 


In  front  of  the  cerebellum  the  tube  is  narrower  and  is  compressed  laterally. 
This  part  is  the  isthmus  (Fig.  447).  Anterior  to  this,  the  roof  plate  and  alar 
plates  expand  into  the  mid-brain  roof,  the  basal  and  floor  plates  forming  the 
basal  part  of  the  mid-brain. 

Certain  gross  changes  which  from  now  on  take  place  in  the  medulla  may 
conveniently  be  noted  here.  At  about  this  time  (fifth  week)  the  outer  borders 
of  the  alar  plate  become  folded  outward  and  then  downward,  being  thus  turned 
back  on  the  plate  itself  (Figs.  452  and  416).  This  fold  is  called  the  primary 
rhombic  lip,  and  is  most  marked  along  the  caudal  border  of  the  cerebellum. 
The  folds  of  the  lip  then  fuse,  forming  a  rounded  eminence  composing  the  border 
of  the  alar  plate  to  which  the  roof  plate  is  attached  laterally.  Subsequently, 
the  attachment  to  the  roof  plate  is  shifted  dorsally  in  the  medulla,  caudally  in 


-D.  IV 


M.I. 


Nu.  IV. 


FIG.  447. — Transverse  section  through  the  isthmus  of  a  10.2  mm.  human  embryo.     D. IV,  Decussa- 
tion  of  trochlear  nerve;  M.I.,  marginal  layer;  Nu.  IV,  nucleus  trochlear  nerve.     His. 

the  cerebellum.  The  portion  of  this  lip  which  thins  off  into  the  roof  plate  is  the 
t&nia  of  the  medulla  and  the  posterior  velum  and  taenia  of  the  cerebellum.  The 
thin  roof  plate  itself  becomes  tbe  epithelial  part  of  the  tela  chorioidea  of  the 
fourth  ventricle.  At  the  caudal  apex  of  the  fourth  ventricle  a  fusion  of  the 
lips  of  the  opposite  sides  forms  the  obex. 

A  further  complication  is  due  to  the  increasing  pontine  flexure  by  which  the 
dorsal  walls  of  the  tube  are  brought  close  together  (Fig.  448) .  The  transverse 
fold  of  the  tela  thus  produced  is  the  chorioid  fold.  At  about  the  same  time 
lateral  pocketings  outward  of  the  dorsal  walls  occur  just  caudal  to  the  cere- 
bellum which  contain  portions  of  the  chorioid  fold.  These  are  the  lateral 
recesses.  By  further  growth  and  vascularization,  the  mesodermal  part  of  the 
chorioid  fold  forms  the  chorioid  plexus  of  the  fourth  ventricle  (metaplexus). 
Finally,  in  the  human  brain  an  aperture  appears  in  the  caudal  portion  of 
the  roof  of  the  ventricle — the  foramen  of  Magendie  (metapore) ;  and,  according 
to  many  authorities,  one  also  occurs  in  the  roof  of  each  of  the  lateral  recesses 


THE  NERVOUS   SYSTEM.  521 

—the  foramina  of  Luschka.  The  roof  of  the  fourth  ventricle,  where  present, 
is  thus  composed  of  an  inner  ependymal  epithelium — the  expanded  roof  plate 
of  the  neural  tube — and  an  outer  mesodermal  covering  containing  blood  vessels. 
Other  gross  changes  chiefly  involve  the  basal  plate.  At  the  beginning  of  the 
fifth  week  this  does  not  much  exceed  the  alar  plate  in  thickness  and  is  separated 
from  the  opposite  basal  plate  by  an  inner  median  sulcus  (Fig.  452).  The  basal 
plate  now  increases  in  thickness  and  thereby  both  deepens  the  sulcus  and  con- 
tributes to  a  flattening  out  of  the  lateral  walls,  so  that  all  portions  by  the  sixth 
week  lie  approximately  in  the  same  horizontal  plane  (Fig.  454).  Later,  the 
floor  plate  increases  in  thickness  more  rapidly  and  the  sulcus  becomes  shallower 
(eight  weeks)  (Fig.  455) .  The  band  of  vertical  ependyma  fibers  passing  through 

Mesencephaion 

A 
Epiphysis. 

Diencephalon -^Sitta^,         '^j^^^^H^IKHL Isthmus 

-  -  Cerebellum 

" '  Transverse  fold 

-  -Rhombic  lip 


Olfactory  lobe 7*-^ 

Optic  stalk •^"3^1  ,y, '     / 


Infundibulum         Hypophysis          Basilar  artery 
FIG.  448. — Lateral  view  of  a  model  of  the  brain  of  a  *]\  weeks'  (18.5  mm.)  human  embryo.    His. 

it  is  the  septum  medulla.  It  is  bounded  on  each  side  by  a  vertical  extension  of 
the  marginal  layer  which  for  convenience  will  be  referred  to  as  the  septal 
marginal  layer  (Figs.  453,  454  and  455). 

The  histological  condition  of  this  part  of  the  tube  at  the  beginning  of  five 
weeks  has  already  been  described.  The  lateral  walls  consist  of  an  inner  layer 
of  closely  packed  cells,  of  a  mantle  layer  consisting  of  efferent  neurones  and  a 
simple  system  of  intermediate  neurones,  and  an  outer  marginal  layer  containing 
the  longitudinal  bundles  of  incoming  afferent  roots  and  longitudinal  axones  of 
intermediate  neurones  (see  p.  511).  It  has  been  seen  that  this  condition  has 
been  brought  about  by  the  proliferation  of  cells  near  the  tube  cavity,  which 
migrate  outward,  at  the  same  time  many  of  them  differentiating  into  neuro- 
blasts  and  nerve  cells  and  thereby  forming  the  mantle  layer.  As  in  the  cord, 
the  basal  plate  takes  the  lead  and  thus  at  first  outstrips  the  alar  plate,  as  shown 


522  TEXT-BOOK  OF  EMBRYOLOGY. 

in  its  greater  thickness  above  mentioned.  This  process  likewise  terminates 
sooner  in  the  basal  plate,  few  cell  divisions  being  present  there  at  seven  weeks. 
At  about  the  end  of  the  fifth  week  (see  p.  526)  the  alar  plate  begins  to  develop 
very  rapidly.  Its  period  of  proliferation  is  about  terminated  at  the  end  of  the 
second  month.  When  the  cell  proliferation  near  the  ventricle  has  ceased, 
the  inner  layer  is  reduced  by  outward  migration  to  a  single  layer  of  ependyma 
cells  (compare  pp.  492  and  493). 

While  the  efferent  nuclei  continue  to  develop  and  the  central  continuations 
of  the  afferent  neurones  continue  to  grow  in  length,  the  principal  differentiations 
now  taking  place  in  the  rhombic  brain  are  those  affecting  the  intermediate 
neurone  systems. 

The  first  of  these  to  be  considered  is  the  further  differentiation  of  the  system 
of  intersegmental  neurones  (p.  472).  The  earlier  development  of  this  system 
has  been  seen  to  involve  especially  the  basal  plate  and  the  further  development 
of  the  latter  leads  to  the  complete  differentiation  of  the  formatio  reticularis 
which  especially  represents  this  system  in  the  epichordal  brain.  It  has  already 
been  seen  (p.  511)  that  many  of  the  intermediate  neurones  representing  the 
beginning  of  this  system  seem  to  be  at  first  heteromeric  and  form  an  internal 
arcuate  system  of  fibers  similar  to  those  seen  in  the  cord  (pp.  510,  514).  They 
increase  in  number  toward  the  median  line  and  are  especially  numerous  in  the 
basal  plate,  where  they,  together  with  the  medial  efferent  neurones  (XII  and 
VI  cranial  nerves),  form  an  eminence  of  the  mantle  layer  corresponding  to  the 
ventral  gray  column  of  the  cord  (Fig.  449).  Many  of  the  axones  of  these  cells 
of  the  arcuate  system  cross  the  septum  medullae,  thus  marking  the  beginning  of 
the  raphe,  and  form  on  each  side  a  longitudinal  bundle  in  the  septal  marginal 
layer  (Fig.  449).  These  longitudinal  bundles  correspond  to  the  first  formation 
of  the  ventral  funiculi  of  the  cord.  They  must  not,  of  course,  be  confused 
with  the  pyramids  which  appear  much  later.  Whether  these  longitudinal 
bundles  are  also  partly  formed  of  axones  of  tautomeric  cells  is  uncertain. 
Later,  as  the  anterior  horn  swellings  grow  and  the  depth  of  the  septum 
medullae  and  of  the  septal  marginal  layers  increases  (compare  p.  521),  more 
longitudinal  fibers  appear  in  the  latter,  the  new  ones  apparently  being  added 
ventrally.  Others  also  appear  more  laterally  in  the  marginal  layer  (Figs.  453, 
454  and  455).  (Compare  cord,  p.  514.)  At  this  time,  also,  fibers  enter  the 
marginal  layer  bordering  the  surface  (as  distinguished  from  the  septal),  pass 
along  parallel  with  the  surface,  cross  the  septum,  and  proceed  to  various  parts 
of  the  marginal  layer  of  the  opposite  side.  These  fibers  are  the  first  external 
arcuate  fibers  as  opposed  to  the  preceding  internal  arcuate  fibers  which  traverse 
the  mantle  layer  (gray)  in  the  arcuate  part  of  their  course  (Fig.  453). 

The  majority  of  the  longitudinal  fibers  entering  the  septal  marginal  layers 
during  the  second  month  occupy  approximately  the  position  of  the  future 


THE  NERVOUS   SYSTEM. 


523 


mesial  formatio  reticularis  alba  (white  reticular  formation)  and  correspond  in 
position  to  the  fibers  of  the  medial  longitudinal  fasciculi  and  reticulo- spinal 
tracts  in  the  adult  medulla,  representing  probably  the  same  system  as  the 
medial  part  of  the  ventro-lateral  funiculi  of  the  cord  (medial  longitudinal 
fasciculi,  reticulo-spinal  and  ventro-medial  ground  bundles  of  the  cord).  The 
medial  longitudinal  fasciculi  are  in  part  descending  fibers  from  higher  levels 
described  later. 


Alar  plate 


Sulcus  limitans 


Basal  plate 


Tsenia  — 


Marginal  layer 

Mantle  layer 
Inner  layer 

Tractus  solitarius 


N.  X. 
(Medullary  XI) 


Internal  arcuate  fibers 

(in  beginning  gray 

reticular  formation) 


N.  XII 


Ventral  funiculus  Floor  plate 

(beginning  of  form,  retic.  alba; 

FIG.  449. — Half  of  a  transverse  section  of  the  medulla  of  a  10.2  mm.  human  embryo.     His. 

In  the  basal  plate,  between  the  medial  and  lateral  efferent  nuclei,  there  are, 
even  at  the  beginning  of  the  fifth  week,  not  only  the  efferent  neurones  and  the 
heteromeric  (commissural)  neurones  already  mentioned,  but  other  neuroblasts 
whose  axones  have  a  radial  direction,  i.e.,  toward  the  periphery.  (Figs.  449 
and  452.)  The  interlacing  of  these  with  the  arcuate  fibers  forms  the  first 
indication  of  the  formatio  reticularis  grisea  (gray  reticular  formation] .  Later, 
longitudinal  fibers  are  present  here,  giving  rise  to  a  condition  more  fully 
corresponding  to  that  in  the  adult,  analogous  also  to  the  condition  in  the 
lateral  funiculi  of  the  cord,  especially  in  the  processus  reticularis. 


524 


TEXT-BOOK  OF  EMBRYOLOGY. 


In  the  region  of  the  auditory  segment  an  important  neurone  group  appears 
which  is  possibly  a  differentiation  of  the  extreme  dorso-lateral  portion  of  the 
basal  plate.  This  is  Deiters'  nucleus,  which  apparently  receives  vestibular 
and  cerebellar  fibers  and  sends  uncrossed  descending  bundles  along  the  outer 
lateral  part  of  the  reticular  formation  and  also  ascending  and  descending  crossed 
and  uncrossed  fibers  along  its  outer  mesial  portion  (part  of  the  medial  longi- 
tudinal fasciculus).  This  nucleus  thus  represents,  apparently,  like  the  nucleus 
ruber  and  nucleus  of  Darkschewitsch  (below),  a  differentiated  portion  of  the 
intersegmental  neurones  in  especial  connection  with  suprasegmental  efferent 
fibers  which  thereby  act  on  many  brain  and  cord  segments. 

The  great  development  of  the  reticular  formation  here  and  caudally  possibly 
causes  a  ventro-lateral  displacement  of  the  contained  nucleus  ambiguus  and 
efferent  facial  nucleus  and  consequently  the  arched  or  hook-shaped  course  of 


© 


sed.  sulcus 


medsulcus 


A  B  C 

FIG.  450. — Diagram  illustrating  the  development  of  the  genu  of  the  facial  nerve  in  the  human 
embryo.  The  drawings  show  the  right  facial  nerve  and  its  nucleus  of  origin,  in  three  stages: 
the  youngest,  A,  being  a  10  mm.  embryo,  and  the  oldest,  C,  a  new-born  child.  The  relative 
position  of  the  abducens  (VI)  nerve  is  represented  in  outline;  its  nerve  trunk  is  not  shown,  as 
the  structures  represented  are  seen  from  above.  Streeter. 

their  root  fibers  as  seen  in  transverse  section  (Streeter).  At  the  same  time,  the 
nucleus  of  the  VI,  which  originally  was  caudal  to  the  VII,  migrates  cranially, 
carrying  the  facial  efferent  roots  with  it.  This  gives  rise  to  the  genu  facialis 
(Streeter,  Fig.  450). 

In  the  mid-brain  (Fig.  451),  what  appears  to  represent  the  basal  plate 
forms  an  eminence,  the  tegmental  swelling.  Later  there  is  differentiated  from 
this  the  reticular  formation  of  this  region,  containing  various  nuclei  and 
traversed  by  radial,  longitudinal  and  arcuate  fibers,  many  of  the  latter  arising 
from  the  later  differentiating  dorsal  portions  (corpora  quadrigemina)  of  the 
lateral  mid-brain  walls.  An  important  neurone  group  of  the  reticular  forma- 
tion system  which  appears  in  this  region  is  the  nucleus  of  Darkschewitsch.  Its 
descending  axones  form  a  part  of  the  medial  longitudinal  fasciculus  and 
probably  appear  at  the  end  of  the  first  month.  The  nucleus  ruber  is  probably 
differentiated  from  the  forward  extremity  of  the  tegmental  swelling  which  over- 
laps into  a  prechordal  region  (Fig.  463).  Its  axones  (crossing  as  ForeVs  decus- 
sation  and  forming  the  rubro-spinal  tract}  probably  develop  early.  This 


THE  NERVOUS   SYSTEM. 


525 


neurone  group  apparently  owes  its  great  development  principally  to  its  close 
association  with  the  cerebellum.  These  two  long  descending  intersegmental 
tracts  as  they  grow  downward  envelop  the  differentiating  reticular  formation 
of  more  caudal  regions  of  brain  (and  cord)  and  thereby  come  to  occupy  an 
external  position  in  the  fully  differentiated  reticular  formation. 

The  reticular  formation  is  thus  composed  of  a  gray  portion  containing  the 
neurone  bodies  and  shorter  tracts  and  a  white  portion  composed  of  the  longer 
tracts.  Axones  from  certain  nuclei  (especially  N.  ruber,  N.  of  Darkschewitsch 
and  N.  of  Deiters)  form  long,  principally  descending,  tracts  which  envelop  the 
gray  reticular  formation  mesially  (medial  longitudinal  fasciculus  including 
fibers  from  nuclei  of  Darkschewitsch  and  Deiters  as  well  as  other  reticulo- 
spinal  fibers)  and  laterally  (rubro-spinal,  lateral  uncrossed  tract  from  Deiters' 


Alar  plate 


Root  fibers  N.  Ill 
FIG.  451. — Transverse  section  through  the  mid-brain  of  a  10.2  mm.  human  embryo.     His. 

nucleus  and  other  reticulo-spinal  fibers)  and  constitute  the  white  reticular 
formation.  These  long  tracts  descend  to  the  cord  and  there  similarly  envelop 
its  ventro-lateral  ground  bundles. 

While  the  above  differentiation  of  the  reticular  formation  has  been  taking 
place,  changes  in  the  alar  plate  have  begun  which  lead  to  the  formation  of 
terminal  nuclei  of  peripheral  afferent  nerves,  as  well  as  terminal  nuclei  of  other 
tracts,  all  of  which  send  fiber  bundles  to  suprasegmental  structures. 

The  formation  of  the  receptive  nuclei  of  the  afferent  nerves  of  peripheral 
(segmental)  structures  is  complicated  by  the  fact  that  the  central  continuations 
of  the  peripheral  afferent  nerves  are  not  confined  to  their  own  respective  seg- 
ments but  form  longitudinal  tracts  which  continue  to  grow  upward  (columns  of 
Goll  and  Burdach)  or  downward  (descending  solitary,  vestibular  and  trigeminal 
tracts)  passing  into  other  segments  and  overlapping  externally  structures 
already  in  process  of  formation  there.  In  each  segment,  then,  the  terminal 
nuclei  of  the  afferent  nerves  of  that  segment  must  be  distinguished  from  the 


526  TEXT-BOOK  OF  EMBRYOLOGY. 

terminal  nuclei  of  afferent  elements  from  other  segments.  The  latter  are 
external  or  added  to  the  former  and  are  differentiated  from  additional  prolifer- 
ations of  neuroblasts  of  the  alar  plate.  In  addition  to  these  nuclei,  there  are 
certain  nuclei  forming  links  between  the  two  great  suprasegmental  structures, 
the  pallium  and  cerebellum.  These  nuclei  are  the  olive*  and  pons  nuclei, 
both  of  which  form  afferent  cerebellar  bundles  and  which  are  differentiated  by 
still  further  proliferations  and  migrations  of  alar  plate  neuroblasts. 

It  has  already  been  seen  that  the  afferent  peripheral  nerves  (IX  and  X) 
of  the  visceral  segment  form  (together  with  descending  fibers  of  the  VII)  the 
tractus  solitarius.  This  is  at  first  (5th  week)  short,  but  in  six  weeks  has  reached 
the  cord.  The  terminal  nucleus  of  the  tractus  solitarius  is  differentiated  from 
the  neuroblasts  of  the  medial  portion  of  the  alar  plate.  The  course  of  the 
axones  of  this  nucleus  is  not  known.  Judging  from  comparative  anatomical 
grounds,  they  would  not  follow  the  fillet  pathway  (C.  J.  Herrick).  The  most 
caudal  part  of  this  nucleus  is  the  nucleus  commissuralis  at  the  lower  apex  of  the 
fourth  ventricle. 

The  formation  of  the  other  terminal  nuclei  lying  in  the  region  of  this  seg- 
ment is  begun  by  the  further  developments  of  the  alar  plate  already  alluded 
to.  These  are  initiated  by  an  expansion  and  consequent  folding  of  its  border 
(formation  of  the  rhombic  lip,  p.  520),  followed  by  further  cell-proliferation, 
leading  to  fusion  of  these  folds  and  copious  formation  of  neuroblasts  in  this 
region.  These  neuroblasts  represent  fresh  accessions  to  the  neuroblasts 
already  formed  in  the  mantle  layer  of  the  more  medial  part  of  the  alar  plate. 
This  latest  development  of  the  border  portions  of  the  alar  plate  is  the  last  step 
in  the  progressive  development  of  the  neural  tube  from  the  medial  portion 
(basal  plate)  to  the  lateral  (dorsal)  border  of  the  lateral  walls  of  the  tube 
where  further  development  ceases  at  the  attachment  to  the  roof  plate  (taenia). 
(Fig.  452.) 

Many  of  the  neuroblasts  of  the  rhombic  lip  region  migrate  ventrally.f 
Some  of  those  from  the  medial  part  of  the  swelling  produced  by  the  fusion  of 
the  rhombic  lip  folds  (p.  520)  migrate  along  the  inner  side  of  the  tractus  soli- 
tarius, while  those  from  the  lateral  part  of  the  swelling  pass  outside  the  tractus, 
which  becomes  thereby  enclosed  in  the  mantle  layer  (Fig.  453).  Many  of  these 
neuroblasts  continue  their  journey,  passing  along  the  outer  side  of  the  differ- 


*This  is  conjectural.  The  origin  of  fibers  to  the  inferior  olivary  nuclei  is  not  known.  The 
most  conspicuous  tract  to  the  olive  is  von  Bechterew's  central  tegmental  tract.  Purely  a  priori  con- 
siderations might  be  adduced  in  favor  of  this  being  considered  a  descending  tract  from  thalamic 
nuclei  which  in  turn  receive  pallio-thalamic  fibers.  It  may,  however,  arisefrom  lower  optic  centers. 

fit  is,  perhaps,  an  open  'question  whether  the  formation  of  the  lip  is  a  fundamental  feature  in 
this  last  proliferation  and  invasion  of  neuroblasts  from  the  border  of  the  alar  plate.  The  promi- 
nence of  the  rhombic  lip  in  man  is  the  early  embryological  expression  of  the  future  great  develop- 
ment of  parts  subsequently  formed  from  this  portion  of  the  neural  wall,  especially  the  cerebellum 
and  neurone  groups  in  connection  with  it. 


THE  NERVOUS   SYSTEM. 


527 


entiating  formatio  reticularis,  until  they  are  arrested  at  the  septal  marginal  layer 
(Figs.  454  and  455). 

From  these  neuroblasts  which  remain  in  situ  near  the  dorsal  border  are  de- 
veloped the  nucleus  gracilis  and  nucleus  cuneatus.  The  axones  of  these  nuclei 
form  internal  arcuate  fibers  which  decussate  and  form  a  bundle  of  longitudinal 
fibers  in  the  opposite  septal  marginal  layer  ventral  to  the  reticularis  alba. 
This  tract  is  the  medial  fillet  whose  fibers  appear  during  the  second  month 
and  is  one  of  the  afferent  paths  to  suprasegmental  structures  (mid-brain  roof 


Inner  rhombic  furrow 

Rhombic  lip 
Outer  rhombic  furrow 
^ —  Alar  plate' 

Sulcus  limitans 

Tractus  solitarius 
Inner  layer 

N.  X  (medullary  XI) 
Mantle  layer 
Marginal  layer 

Basal  plate 

Beginning  of  gray 
reticular  formation 


Floor  plate  F.r.a.  N.  XII  Internal  arcuate  fibers 

(forming  septum  medullas) 

FIG.  452. — Half  of  a  transverse  section  of  the  medulla  of  a  9.1  mm.  human  embryo 

(during  the  fifth  week).     His. 
The  arrow  is  in  the  inner  median  sulcus.     F.  r.  a.,  beginning  of  white  reticular  formation. 

and  pallium).  Other  neuroblasts,  which  probably  migrate  further,  form  the 
substantia  gelatinosa  of  Rolando.  Axones  of  this  group  also  form  tracts  repre- 
senting afferent  paths  to  suprasegmental  structures  (pallium).  Neuroblasts 
which  migrate  further  form,  as  already  mentioned,  afferent  cerebellar  con- 
nections. Those  migrating  to  the  septal  marginal  layer  form  there  an 
L-shaped  mass  mesial  to  the  root  fibers  of  the  XII  cranial  nerve  (Fig.  455). 
This  is  the  medial  accessory  olive.  Fresh  groups  of  neuroblasts,  added  laterally 
to  these  in  streaks,  form  the  inferior  olivary  nucleus,  while  others  which  have  not 
advanced  so  far  form  the  lateral  nucleus.  Axones  of  the  olivary  neuroblasts 

34 


528 


TEXT-BOOK  OF  EMBRYOLOGY. 


(olivo-cerebellar  fibers)  pass  across  the  median  line  (seventh  or  eighth  week)  to 
the  opposite  dorsal  border  where  they,  together  with  axones  from  the  lateral 
nuclei  and  the  continuation  from  the  cord  of  Flechsig's  tract,  form  (end  of 
the  second  month)  the  bulk  of  the  restiform  body  (Fig.  455).  At  three  months 
the  olives  have  acquired  their  characteristic  folded  appearance. 

Owing  to  the  later  development  and  ventral  migration  of  the  alar  plate 
neuroblasts,  there  are  thus  formed  the  various  nuclei  which  lie  external  to  the 
reticular  formation  in  the  adult.  The  continuations  of  ascending  spinal  cord 


Outer  part  of  rhombic 
lip  migration 

Inner  part  of  r.  1.  mig. 
Inner  layer 
Tractus  solitarius 
Marginal  layer 
Mantle  layer 

Ext.  arcuate  fibers 
Int.  arcuate  fibers 


Septum      Beginning  white        N.  XII       Gray  reticular 
medullae    reticular  formation  formation 

FIG.  453. — Half  of  a  transverse  section  of  the  medulla  of  a  10.5  mm.  human  embryo 
(end  of  fifth  week).     His. 

tracts  (Flechsig  and  Gowers)  occupy  the  most  external  position  on  the  lateral  sur- 
face, and  other  cord  continuations  (medial  fillets)  the  most  external  mesial 
positions.  Later,  however  (fifth  month),  there  is  added  ventral  to  the  fillets 
the  descending  cortico-spinal  fibers  (pyramids).  Their  decussation  takes 
place  at  the  cervical  flexure. 

By  the  external  accessions  from  the  alar  plate  above  described,  forming 
terminal  nuclei  of  overlapping  tracts  from  above  (especially  the  nucleus  of 
the  spinal  V),  the  tractus  solitarius  becomes  buried,  as  it  were,  hence  its  deep 
position  in  the  adult.  The  great  development  of  the  reticular  formation 
may  contribute  to  this  result.  As  the  trigeminus  is  the  most  cephalic  rhombic 


THE  NERVOUS   SYSTEM. 


529 


segment,  its  descending  fibers  are  not  overlapped  by  fibers  from  above  and 
therefore  occupy  the  most  external  position  of  all  these  descending  peripheral 
systems. 


Inner  layer        Gray  ret.  form 
I 


F.r.a. 


Rhombic  lip  migration 

Ext.  arc.  fib.  in  marg.  layer        N.  XII        F.r.a. v.        Septum  medullae 

FIG.  454. — Half  of  a  transverse  section  through  the  medulla  of  a  13.6  mm.  human  embryo 

(beginning  of  sixth  week).     His. 

F.  r.  a.,  Beginning  of  white  reticular  formation  in  dorsal  part  of  septal  marginal  layer. 
Another  bundle  has  termed  more  ventrally  (F.  r.  a.  v.) . 


Inner  layer 


Roof  plate 


Tractus  solitarius 


Formatio  reticularis 
grisea 


Formatio  reticularis  alba 


N.  XII  Septum 

medullae 


Spinal  V 

Neuroblasts  from  alar  plate 
Marginal  layer 


Neuroblasts  from  alar  plate 
(Rudiment  of  accessory  olive) 


FIG.  455. — Transverse  section  through  the  medulla  of  an  8  weeks'  human  embryo.     His. 

The  terminal  nuclei  belonging  to  the  auditory  (acustico-facialis-abducens) 
segment  are  those  of  the  vestibular  and  cochlear  portions  of  the  VIII  nerve. 


530  TEXT-BOOK  OF  EMBRYOLOGY. 

The  development  of  these  nuclei  is  not  fully  known,  but  they  are  derived  from 
the  alar  plate,  except  possibly  Deiters'  nucleus  (see  p.  524),  the  nuclei  of  the 
later  formed  cochlear  nerve  occupying  the  more  external  position.  The  ves- 
tibular  nuclei  apparently  send  axones  both  to  cerebellum  and  reticular  formation. 
The  cerebellum  itself  may  be  regarded  as  primitively  a  receptive  vestibular 
structure  (p.  473)  and  probably  receives  vestibular  root  fibers.  The  axones 
of  the  cochlear  nuclei  pass  across  the  median  line,  along  the  ventral  border  of 
the  reticular  formation  (second  half  of  second  month),  forming  the  trapezium. 
On  the  lateral  boundary  of  the  opposite  reticular  formation  they  ascend,  form- 
ing the  lateral  fillet,  to  the  suprasegmental  posterior  corpus  quadrigeminum. 
Accessions  are  received  from  the  superior  olive,  in  which  some  of  the  trapezium 
fibers  terminate. 

The  alar  plate  of  this  segment  also  forms  the  substantia  gelatinosa  and  the 
anterior  portions  of  the  olivary  nuclei  in  this  region.  The  various  remaining 
tracts  assume  the  same  positions  as  further  caudally. 

Later,  the  pyramids  are  added  ventrally  to  the  fillet,  and  the  great  develop- 
ment of  the  pons  leads  to  its  covering  the  ventral  surface  of  part  of  this  region. 
Owing  to  the  late  development  of  the  pons  and  pyramids,  the  trapezium  is  thus 
uncovered  and  lies  on  the  ventral  surface  of  the  rhombic  brain  during  the  third 
month.  It  is  permanently  uncovered  in  the  dog  and  cat. 

In  the  trigeminus  segment,  the  terminal  nucleus  of  the  afferent  portion  of 
this  nerve  is  probably  similarly  formed  from  the  alar  plate.  Its  axones  decus- 
sate, probably  joining  the  fillet,  and  proceed  to  the  thalamus,  which  is  connected 
with  the  pallium.  Descending  axones  from  cells  in  the  mid-brain  roof  form 
part  of  the  trigeminus  known  as  its  descending  or  mesencephalic  root.  The 
view  has  been  advanced  (Meyer,  Johnston)  that  these  are  afferent  neurones 
equivalent  to  certain  dorsal  horn  cells  found  in  some  adult  and  embryonic 
Vertebrates  and  representing  spinal  ganglion  cells  which  have  become  included 
in  the  neural  tube  instead  of  becoming  detached  with  the  rest  of  the  neural  crest 
(compare  p.  459). 

In  front  of  the  lateral  recess  another  extensive  development  of  the  alar  plate 
occurs,  evidenced  by  the  large  rhombic  lip  of  this  region.  The  neuroblasts 
thus  differentiated  form  the  enormously  developed  pantile  nuclei  whose  axones 
pass  across  the  median  line  (fifth  month)  to  the  opposite  cerebellar  hemisphere, 
forming  the  middle  cerebellar  peduncle  or  brachium  pontis.  The  pons  extends 
over  the  ventral  surface  of  the  cephalic  part  of  the  medulla  and  over  the  ventral 
surface  of  part  of  the  mid-brain.  It  receives  fibres  from  various  parts  of  the 
neopallium,  which  form  a  great  part  of  the  pes  pedunculi  or  crusta.  A  still 
greater  development  of  the  alar  plate  forms  the  cerebellum. 

In  the  mid-brain  region,  the  reticular  formation  already  described  (p.  524) 
is  enveloped  ventrally  and  laterally  by  the  upward  extension  of  the  medial  and 


THE  NERVOUS   SYSTEM.  531 

lateral  fillets,  the  whole  comprising  the  legmentum.  Ventral  to  this  are  added 
later  the  pons  and  the  descending  cortico-pontile,  cortico-bulbar  and  cortico- 
spinal  bundles  forming  here  the  pes  pedunculi  or  crusta  (probably  during  the 
fifth  month). 

The  alar  plate  of  the  mid-brain  region  forms  the  corpora  quadrigemina 
(mid-brain  roof). 

The  further  changes  in  the  gross  morphology  of  the  medulla  are  due  mainly 
to  further  growth  of  structures  already  present.  The  nuclei  of  the  dorsal  col- 
umns by  their  increase  cause  the  swellings  on  the  surface  of  the  medulla  known 
as  the  dava  and  cuneus,  and  likewise  by  their  increase  in  size  cause  a  secondary 
dorsal  closing  in  of  the  caudal  apex  of  the  fourth  ventricle  which  formerly 
extended  to  the  cervical  flexure.  The  tuberculum  of  Rolando  is  produced  by  the 
growth  of  the  terminal  nucleus  of  the  spinal  V,  and  the  restiform  body  largely 
by  the  development  of  the  afferent  cerebellar  fibers  (Fig.  457). 

The  growth  of  the  olivary  nuclei  produces  the  swellings  known  as  the 
olives.  The  above  mentioned  accession  of  the  descending  cerebrospinal  tracts 
to  the  ventral  surface  is  indicated  by  the  pyramids. 

In  the  floor  of  the  ventricle  there  is  a  longitudinal  ridge  each  side  of  the 
median  line  occupied  by  swellings  produced  by  the  nucleus  of  the  XII  and, 
further  forward,  the  nucleus  of  the  VI,  together  with  other  nuclei  (intercalatus, 
funiculus  teres  and  incertus,  Streeter)  which  are  not  well  understood.  The 
furrow  forming  the  lateral  boundary  of  this  area  is  usually  taken  to  be  the 
representative  of  the  sulcus  limitans  and  consequently  the  area  in  question 
would  be  the  basal  plate.  Lateral  to  it  is  a  triangular  area  with  depressed 
edges — the  ala  cinerea.  It  represents  a  region  where  portions  of  the  vago- 
glossopharyngeal  nuclei  (dorsal  efferent  and  terminal  nuclei  of  fasciculus 
solitarius)  lie  near  the  surface.  Possibly  a  secondary  invasion  by  surrounding 
more  recently  differentiated  nuclei  may  account  for  their  apparent  partial 
retreat  from  the  surface.  It  is  possible  that  the  ala  cinerea  may  be  regarded 
not  so  much  as  a  part  of  the  alar  plate,  but  that  it — or  rather  the  branchial 
nuclei  involved  in  its  formation — represents  an  independent  intermediate  region 
corresponding  to  the  intermediate  region  in  the  cord  (J.  T.  Wilson).  The 
remaining  portion  of  the  alar  plate,  in  the  floor,  is  apparently  represented 
principally  by  the  acoustic,  especially  the  vestibular,  field. 

In  the  development  of  the  segmental  brain  there  are  thus  the  following 
overlapping  stages:  (i)  The  differentiation  of  the  inner,  mantle  and  marginal 
layers.  (2)  The  primary  neural  apparatus,  consisting  of  (a)  the  peripheral 
segmental  neurones,  the  central  processes  of  the  afferent  neurones  entering  the 
alar  or  receptive  plate,  the  efferent  neurone  bodies  forming  two  main  series 
of  nuclei  in  the  basal  plate,  and  (b)  intersegmental  neurones  composing  the 
reticular  formation  in  which  the  long  tracts  occupy  external  positions.  (3) 


532 


TEXT-BOOK  OF  EMBRYOLOGY. 


The  further  differentiation,  from  the  alar  plate,  of  terminal  nuclei  for  the 
afferent  peripheral  segmental  neurones,  the  axones  of  the  terminal  nuclei 
forming  afferent  tracts  to  suprasegmental  structures.  These  tracts  and  other 
later  forming  afferent  suprasegmental  tracts  with  their  nuclei  are  laid  down 
external  to  the  reticular  formation.  (4)  Formation  of  efferent  (chiefly  thala- 
mic(?)  mid-brain  and  cerebellar)  suprasegmental  tracts  which  act  upon  the 
intersegmental  neurones  or  reticular  formation.  (5)  Accession  at  a  late  stage 
of  development  of  a  descending  system  of  fibres  from  the  neopallium.  These 
lie  ventral  to  the  preceding  structures. 


Jl 


The  Cerebellum. 

It  has  already  been  pointed  out  that  at  an  early  period  (three  weeks)  the 
anterior  boundaries  of  the  thin  expanded  roof  plate  of  the  rhombic  brain  form 
two  lines  converging  anteriorly  to  the  median  line  where 
the  roof  plate  is  represented  by  the  usual  narrow  portion 
connecting  the  two  alar  plates  (Fig.  456).  It  has  also 
been  pointed  out  that  the  pontine  flexure  produces  on  the 
dorsal  surface  a  deep  transverse  fold  in  this  thin  roof,  into 
which  vascular  tissue  grows  later  forming  the  chorioid 
plexus  (Fig.  448).  At  this  stage,  the  continuations  of  the 
alar  plates  of  the  medulla  form  two  transverse  bands 
which,  when  viewed  laterally,  are  vertical  to  the  general 
longitudinal  axis  of  this  part  of  the  brain  (Fig.  448) .  At 
the  same  time,  the  rhombic  lips  are  formed  along  the 
caudal  border  of  these  bands  and  the  latter  become 
thickened  into  the  two  rudiments  of  the  cerebellum,  a 
considerable  portion  of  which  may  be  derived  from  the 
lips.  These  rudiments  are  thus  two  transverse  and 
vertical  swellings  and  are  connected  across  the  median 
line  by  the  roof  plate.  The  attachment  (taenia)  of  the 
alar  plate  of  this  region  to  the  roof  plate  of  the  fourth 
ventricle  is  at  first  along  its  caudal  edge.  Later,  by  the 
folding  back  and  fusion  of  this  border  to  form  the  rhom- 
bic lips,  the  attachment  is  carried  forward.  Still  later, 
by  the  growth  of  the  cerebellar  rudiment,  it  is  rolled 
backward  and  under,  as  described  below.  The  rudi- 
ments subsequently  fuse  across  the  median  line,  thus 
forming  externally  a  single  transverse  structure,  but  internally  a  paired  dorsal 
median  projection  of  the  lumen  marks  the  location  of  the  uniting  roof  plate 
(comp.  Fig.  458). 


FIG.  456. — Dorsal  view 
of  that  part  of  the 
brain  caudal  to  the 
cephalic  flexure 
(human  embryo  of  30! 
week.  2.15  mm.).  Hh. 
Cerebellum;  J,  isth- 
mus; M,  mid-brain; 
Rf,  Nh,  med  ulla. 
Compare  with  Fig. 
416.  His. 


THE   NERVOUS   SYSTEM. 


533 


While  the  structure  thus  formed  expands  enormously  in  a  lateral  direction, 
in  its  subsequent  development  its  greatest  growth  is  in  a  longitudinal  direction. 
The  effect  of  this  is  that  the  continuations  of  the  cerebellum  forward  (velum 
medullare  anterius)  and  backward  (velum  medullare  posterius)  into  the  adjoining, 
brain  walls  of  the  isthmus  and  medulla  are  comparatively  fixed  points  and  are 
completely  overlapped  by  the  spreading  cerebellum,  producing  an  appearance 
in  sagittal  section  as  though  they  were  rolled  in  under  the  latter  structure  (comp. 
Fig.  408,  F).  Another  result  of  this  longitudinal  growth  is  the  formation  of  fis- 
sures running  across  the  organ,  transversely  to  the  longitudinal  brain  axis. 
First,  lateral  incisures  separate  two  caudal  lateral  portions,  the  flocculi  (Fig. 
457),  the  median  continuation  of  which,  the  nodule,  is  finally  rolled  in  on 
the  under  side  of  the  cerebellum  as  explained  above.  Another  transverse  fissure, 
the  primary  fissure,  beginning  in  the  median  part  and  extending  laterally,  sepa- 

Cerebellar  hemisphere 


Tasnia 


Tuberculum  cuneatum  - 

Clava 

Tuberculum  cir.ereum  (Rolando) 


—  Vermis 

Eminentia  teres 

''  Tasnia 

Fasciculus  gracilis  (Goll) 
, Fasciculus  cuneatus  (Burdach) 


FIG.  457. — Dorsal  view  of  the  cerebellum  and  medulla  of  a  5  months'  human  foetus.     Kollmann. 

rates  an  anterior  lobe  from  a  middle  lobe,  the  former  comprising  the  future  lin- 
gula,  centralis  and  culmen  and  their  lateral  extensions.  The  anterior  portion 
is  rolled  forward  under  the  anterior  part  of  the  cerebellum.  Another  trans- 
verse fissure  next  appears  in  the  median  part  (secondary  fissure]  which  later  ex- 
tends (peritonsillar)  to  the  floccular  incisure,  and  thereby  completes  the  de- 
marcation of  a  posterior  lobe,  including  not  only  the  flocculus  and  nodule,  but 
also  the  tonsilla  and  uvula,  which  are  also  rolled  backward  and  under.  The 
result  of  this  transverse  fissuration  would  be  the  production  of  a  cerebellum 
resembling  that  of  certain  forms  below  Mammals  where  the  cerebellum  is  well 
developed  (Selachians,  Birds).  A  complicating  factor,  however,  is  the  great 
growth  of  certain  lateral  portions  of  the  middle  lobe,  forming  the  future  cere- 
bellar  hemispheres  (Fig.  457),  which  causes  also  a  lateral  overlapping  and  rolling 
inward  of  adjoining  parts.  This  growth  is  the  chief  factor  in  the  division 
of  the  cerebellum  into  vermis  and  hemispheres  and  is  correlated  with  the  devel- 
opment of  the  neopallium  (p.  473  and  Fig.  409). 


534  TEXT-BOOK  OF  EMBRYOLOGY. 

The  early  histological  development  of  the  cerebellum  has  been  most  closely 
studied  in  Bony  Fishes  (Schaper)  and  there  is  every  reason  to  suppose  that 
the  processes  taking  place  in  the  human  cerebellum  are  essentially  the  same.  In 
that  part  of  the  alar  plate  forming  the  rudiment  above  described,  the  cells  pro- 
liferate, forming  first  a  nuclear  layer  with  the  dividing  cells  along  its  ventricular 
surface,  and  a  non-nucleated  outer  or  marginal  layer.  Later,  owing  to  begin- 
ning migration  and  differentiation,  there  is  formed  the  usual  mantle  layer, 
representing  a  differentiation  of  part  of  the  original  nuclear  layer  and  thereby 
forming  the  three  layers :  an  inner,  a  mantle  and  a  marginal.  The  outer  cells 
of  the  mantle  layer  increase  in  size  and  differentiate  into  the  cells  of  Purkinje, 
smaller  cells  within  forming  the  granular  layer.  The  earliest  stage  of  differ- 
entiation of  the  Purkinje  cells  has  not  been  accurately  described,  but  the  axones 


FIG.  458. — Diagram  representing  the  differentiation  and  migration  of  the  cerebellar  cells  in  a  teleost. 
The  arrows  indicate  the  migration  of  cells  from  the  borders  of  the  cerebellar  rudiment  into 
the  marginal  layer;  these  cells  probably  all  differentiate  into  nerve  cells.  Clear  circles,  indif- 
ferent cells;  circles  with  dots,  neuroglia  cells  (except  in  marginal  layer);  shaded  cells,  epithelial 
cells;  circles  with  crosses,  epithelial  cells  in  mitosis  (germinal  cells) ;  black  cells,  neuroblasts;  L 
lateral  recess;  M,  median  furrow,  above  which  is  roof  plate;  R,  floor  of  4th  ventricle  (IV). 
Schaper. 

of  the  neuroblasts  evidently  proceed  (end  of  fifth  month)  toward  the  ventricular 
surface  instead  of  entering  the  marginal  layer.  In  this  way  the  fibrous  layer 
(white  matter)  comes  to  lie  within  instead  of  on  the  outer  surface  as  in  the  cord, 
and,  to  some  extent,  in  the  medulla.  There  is  thus  formed  the  outer  gray  matter 
or  cortex.  The  axones  of  the  Purkinje  cells  form  the  great  bulk  of  the  centrifu- 
gal fibers  of  the  cerebellar  cortex.  The  marginal  layer  becomes  ultimately 
the  outer  or  molecular  (plexiform)  layer  of  the  adult  cerebellum. 

It  has  been  seen  that  in  the  other  parts  of  the  tube  development  begins  in 
the  medial  parts  of  the  lateral  plates  and  thence  advances  toward  their  dorsal 
borders,  which  actively  develop  after  the  corresponding  stages  have  ceased  in 
the  medial  portions.  The  same  is  true  of  the  cerebellar  ludiment.  In  this, 
the  edges  which  border  on  the  thin  roof  plate,  i.e.,  those  parts  adjoining  the 
lateral  recesses,  the  main  roof  of  the  fourth  ventricle  and  the  roof  plate  inter- 
posed between  the  two  original  lateral  cerebellar  rudiments,  are  the  last  to  pro- 


THE   NERVOUS   SYSTEM. 


535 


liferate.  The  cells  thus  formed  spread  into  the  marginal  layer  of  the  earlier 
developed  parts  and  by  further  proliferation  form  a  nucleated  layer  of  consider- 
able thickness  (Fig.  458).  This  complication  is  apparently  essentially  similar 
to  that  described  above  in  the  development  of  the  medulla.  From  the  cells  of 
this  invasion  are  formed  a  part,  at  least,  of  the  granule  cells,  as  well  as  the  basket 
cells  and  other  cells  which  remain  in  the  marginal  (molecular)  layer.  These 
are  all  association  cells  of  the  cerebellum. 

The  cerebellum  reaches  its  full  histological  development  very  late;  after 
birth  in  many  Mammals.     These  last  postnatal  stages  of  development  naturally. 


D 


K 


FIG.  459. — Scheme  showing  the  various  stages  of  position  and  form  in  the  differentiation  of  granule 
cells  from  the  outer  granular  layer.  Cajal. 

A,  Layer  of  undifferentiated  cells;  B,  layer  of  cells  in  horizontal  bipolar  stage;  C,  partly  formed 
molecular  (plexiform)  layer;  D,  granular  layer;  b,  beginning  differentiation  of  granule  cells; 
c,  cells  in  monopolar  stage;  d,  cells  in  bipolar  stage;  e,f,  beginning  of  descending  dendrite 
and  of  unipolarization  of  cell;  g,  h,  i,  different  stages  of  unipolarization  or  formation  of  single 
process  connecting  with  the  original  two  processes;  /,  cell  showing  differentiating  and  com- 
pleted dendrites;  k,  fully  formed  granule  cell. 

involve  principally  those  cells  proliferated  last  and  which  lie  in  the  mar- 
ginal layer.  These  have  been  studied  by  means  of  the  Golgi  method  in 
new-born  Mammals  by  Cajal  and  others.  The  majority  of  these  cells  form 
granule  cells  by  means  of  a  progressive  migration  and  differentiation,  as  shown 
in  the  accompanying  Fig.  459.  Each  cell  first  develops  a  single  horizontal 
process,  then  another,  thus  becoming  a  horizontal  bipolar  cell.  Following  this, 
the  cell  body  migrates  past  the  Purkinje  cells  into  the  granular  layer,  remaining 
in  connection  with  the  original  processes  by  a  single  process.  There  are  thus 
formed  the  axone  of  the  granule  cell  with  its  bifurcation  into  two  horizontal  pro- 
cesses, the  parallel  fibers  of  the  molecular  layer.  This  mode  of  formation  is  thus 


536 


TEXT-BOOK  OF  EMBRYOLOGY. 


similar  to  the  unipolarization  of  the  cerebrospinal  ganglion  cell.  The  dendrites 
begin  to  be  formed  during  the  migration,  branch  when  the  cell  body  reaches  the 
granular  layer  and  there  finally  attain  the  adult  form.  Other  undifferentiated 
cells  in  the  marginal  layer  send  out  horizontal  processes  the  collaterals  of  which 
envelop  the  Purkinje  cell  bodies,  and  form  the  baskets.  The  place  vacated,  so  to 
speak,  by  the  migrating  granules,  is  filled  at  the  same  time  by  the  developing 
dendrites  of  the  Purkinje  cells.  These  at  first  show  no  regularity  of  branching, 
but  subsequently  differentiate  into  the  definite  branches  of  the  adult  condition, 
at  the  same  time  advancing  toward  the  periphery  (Fig.  460).  When  they 


FIG.  460. — Section  through  cerebellar  cortex  of  a  dog  a  few  days  after  birth,  showing  the  partial 
development  of  the  dendrites  of  two  cells  of  Purkinje.  Cajal. 

A,  external  limiting  membrane;  B,  external  (embryonic)  granule  layer;  C,  partly  formed  molecular 
(plexiform)  layer;  D,  granular  layer;  a,  body  of  cell  of  Purkinje;  b,  its  axone;  c,  and  d,  col- 
laterals with  terminal  arborizations  (e). 

reach  this,  the  migration  of  the  granules  is  completed  and  the  molecular  layer 
is  definitely  formed.  This  condition,  evidenced  by  the  disappearance  of  the 
outer  granular  layer,  is  usually  reached  in  Mammals  within  two  months  after 
birth,  but  in  man  not  until  the  sixth  or  seventh  year.  There  are  observations 
indicating  that  animals  possessing  completely  developed  powers  of  locomotion 
and  balancing  at  birth  have  more  completely  differentiated  cerebella  at  that 
time.  The  axones  of  the  Purkinje  cells  form  many  embryonic  collaterals  which 
are  afterward  reduced  in  number.  * 

Of  the  centripetal  fibers  to  the  cerebellum,  those  from  the  inferior  olives 
cross  the  median  line  of  the  medulla  about  the  seventh  or  eighth  week,  and 
thence  advance  to  the  vermis,  reaching  their  final  destination  during  the  third 


THE   NERVOUS   SYSTEM.  537 

month.  The  fibers  from  the  pontile  nuclei  (middle  peduncle)  do  not  develop 
until  considerably  later  (end  of  the  fourth  month),  the  time  of  their  reaching 
their  destination  in  the  cerebellar  hemispheres  not  being  definitely  known. 
Many  at  least  of  the  centripetal  fibers  do  not  reach  their  full  development  in 
Mammals  till  birth  or  after.  Some  of  these  fibers  (climbing fibers)  form  arbor- 
izations around  the  inferior  (axone)  surface  of  the  Purkinje  cell  bodies  and 
later  creep  upward,  enveloping  the  upper  surface  instead,  and  finally  the  den- 
dritic branches.  Other  centripetal  fibers  (mossy  fibers]  ramifying  in  the 
granular  layer  are  varicose  fibers,  at  first  otherwise  smooth.  From  the  vari- 
cosities  a  number  of  branches  are  given  off  which  later  become  abbreviated  and 
modified  into  the  shorter  processes  of  the  adult  condition.  This  final  differ- 
entiation occurs  simultaneously  with  the  final  differentiation  of  the  dendrites 
of  the  granule  cells  with  which  they  come  into  connection.  The  glia  elements 
apparently  develop  in  a  manner  essentially  similar  to  their  development  else- 
where. 

The  development  of  the  internal  nuclei  of  the  cerebellum  has  not  been 
thoroughly  investigated.  The  nucleus  dentaius  is  well  developed  at  the  end 
of  the  sixth  fcetal  month.  Eminences  passing  forward  and  ventrally  along 
the  sides  of  the  isthmus  are  the  earliest  indications  of  the  superior  peduncles, 
formed  later  by  the  axones  of  the  cells  of  these  nuclei. 

Corpora  Quadrigemina. 

The  mid-brain  roof  is  an  expansion  of  the  alar  plate  of  the  mid-brain. 
Later  this  differentiates  into  the  anterior  and  posterior  corpora  quadrigemina. 
In  the  former,  by  the  usual  ventricular  mitoses  (germinal  cells),  a  nuclear 
layer  is  formed  with  a  non-nucleated  marginal  layer  external  to  it  which  becomes 
the  outer  or  zonal  layer.  Still  later  the  neuroblast  or  mantle  layer  is  differen- 
tiated, there  being  an  unusually  thick  inner  layer.  The  further  development 
has  not  been  closely  studied  in  man.  Owing  to  the  diminished  importance 
of  the  anterior  corpora  quadrigemina  (p.  474)  the  neuroblasts  do  not  differ- 
entiate into  the  well  marked  "spread  out"  layers  characteristic  of  the  optic 
lobes  of  many  Vertebrates.  This  is  probably  due  to  a  lack  of  development  of 
their  association  neurones. 

The  fibers  of  the  optic  tracts  grow  toward  the  anterior  corpora  quadrigemina 
in  the  marginal  layer  forming  the  anterior  brachia.  When  they  reach  the 
anterior  corpora  quadrigemina,  they  leave  the  marginal  layer  and  penetrate 
the  gray  matter  forming  the  most  external  fiber  layer.  The  medial  (and  some 
lateral)  lemniscus  fibers  enter  more  deeply  than  the  optic.  Neuroblast  axones 
grow  toward  the  ventricle,  turn  internally  to  the  lemniscus  fibers,  cross  (Mey- 
nerfs  decussation) ,  and  proceed  as  the  predorsal  tracts  to  the  segmental  brain 
and  cord,  lying  ventral  to  the  medial  longitudinal  fasciculi. 


538  TEXT-BOOK  OF  EMBRYOLOGY. 

The  Diencephalon. 

The  stage  of  development  of  the  diencephalon  at  four  weeks  has  already 
been  mentioned  (p.  485).  (Figs.  461,  471  and  472.)  In  the  lateral  walls  the 
principal  feature  is  the  presence  of  a  furrow,  the  sulcus  hypothalamicus,  which 
begins  ventrally  as  an  extension  of  the  optic  recess  and  extends  dorsally  and 
caudally  toward  the  mid-brain.  A  branch  of  it  extends  to  the  posterior  part 
of  the  foramen  of  Monro.  This  is  the  sulcus  Monroi.  The  sulcus  hypothala- 
micus  is  sometimes  regarded  as  the  representative  in  this  region  of  the  sulcus 
limitans.  It  is  doubtful  whether  it  has  the  same  morphological  value  as  the 
latter.  Such  a  comparison  is  seen  a  priori  to  be  difficult  when  it  is  considered 
that  this  region  is  in  the  most  highly  modified  part  of  the  brain  tube,  lacking 


Ma. 


FIG.  461. — Transverse  section  through  the  diencephalon  of  a  5  weeks'  human  embryo.  Dp.,  Roof 
plate;  Ma.,  mammillary  recess;  P.  s.  hypothalamus;  S.M.,  sulcus  hypothalamicus;  Th., 
thalamus.  His. 

motor  peripheral  apparatus,  and  that  it  is  also  the  end  region  of  the  tube  where 
all  longitudinal  divisions  would  naturally  merge.  The  sulcus  deepens  till  the 
end  of  the  second  month  (Fig.  467).  Later  it  becomes  shallower,  but  appears 
to  persist  till  adult  life.  The  region  of  the  diencephalon  ventral  to  the  sulcus, 
as  already  mentioned,  is  termed  the  pars  subthalamica  or  hypothalamus.  The 
ventral  part  of  the  optic  stalk  forms  a  transverse  groove  in  the  floor,  the  pre- 
optic  recess,  caudal  to  which  is  a  ridge  or  fold,  the  chiasma  swelling,  in  which  the 
fibers  of  the  optic  chiasma  later  appear.*  Caudal  to  this  is  the  recess  or  invagi- 
nation  of  the  floor,  representing  the  postoptic  recess  and  the  beginning  of  the 
infundibulum  (Figs.  462  and  463) .  Its  extremity  later  becomes  extended  into  the 
infundibular  process,  the  posterior  part  of  which  in  the  fifth  week  comes  into 
contact  with  the  hypophyseal  (Rathke's)  pouch.  This  is  a  structure  formed 

*  According  to  Johnston,  the  chiasma  is  formed  in  front  of  the  optic  recess  which  would  then  be 
represented  by  the  postoptic  recess.  In  this  case  the  chiasma  would  be  regarded  as  falling  in  the 
region  of  the  telencephalon  instead  of  forming  the  optic  part  of  the  hypothalamus  (comp.  Figs.  402 
and  471). 


THE   NERVOUS   SYSTEM. 


539 


from  the  stomodaeal  epithelium  and  is  connected  with  the  latter  by  a  stalk. 
The  pouch,  which  is  at  first  a  flat  structure,  develops  two  horns  which  envelop 


Ant.  corp.  quad.    Pineal  Anterior 

(ant.    colliculus)    region          brachium 


Pallium 

Ant. 
Post. 
Optic  stalk 
Hypophyseal  pouch 


olfact.  lobe 


Mammillary    Lateral          Tuber 
region        geniculate    cinereum 
body 

FIG.  462. — Lateral  view  of  a  model  of  the  brain  of  a  10.2  mm.  human  embryo 
(middle  of  5th  week).     His. 

the  infundibulum.  The  cavity  of  the  end  of  the  infundibular  process  becomes 
nearly  shut  off  from  the  rest  of  the  infundibular  cavity.  The  process  penetrates 
the  upper  part  of  the  pouch  and  then  bending  reaches  its  posterior  surface  and 

Diencephalon        Thalamus  Pineal  region 


Pallium 

Foramen  of  Monro 

Sulcus  hypothal- 
amicus 

Ant.  olfact.  lobe 

Post,  olfact.  lobe 

Lamina  terminalis 

Corpus  striatum 


Mesencephalon 
Tegmental  swelling 

Mammillary  region 
Hypothalamus 
Tuber  cinereum 


Recessus      Hypophyseal      Recessus 
(prae?)  opticus        pouch  infundibuli 

FIG.  463. — Median  view  of  the  right  half  of  a  model  of  the  brain  of  a  10.2  mm.  human  embryo 
(middle  of  5th  week).     Compare  Fig.  462.     His. 

ends  blindly.     In  the  second  half  of  the  second  month  epithelial  sprouts,  which 
become  very  vascular,  begin  to  appear,  first  in  the  lateral  parts  of  the  pouch, 


540  TEXT-BOOK  OF  EMBRYOLOGY. 

next  the  brain,  and  then  extending  through  the  pouch  and  finally  nearly  oblit- 
erating its  cavity  (third  month) .  The  shape  of  the  organ  (the  hypophysis) 
formed  by  the  union  of  these  two  parts  is  subsequently  changed  by  its  relations 
to  surrounding  parts.  Its  posterior  lobe  is  derived  from  the  infundibular  por- 
tion, its  anteiior  lobe  from  the  pouch. 

An  expansion  of  the  floor  of  the  brain  caudal  to  the  infundibulum  has  been 
mentioned  as  the  mammillary  region.  Subsequently  there  is  formed  from  its 
cephalic  part  another  evagination,  the  tuber  cinereum.  The  mammillary  region 
forms  the  mammillary  bodies.  The  region  caudal  to  the  mammillary  region 
later  receives  many  blood  vessels,  thereby  becoming  the  posterior  perforated 
space. 

At  the  end  of  the  fourth  week  the  roof  plate  of  the  diencephalon  is  smooth. 
At  about  this  time  the  greater  part  of  the  roof  expands,  forming  a  median 
longitudinal  ridge  (Fig.  464).  This  ridge,  which  remains  epithelial  throughout 
life,  is  broader  at  its  anterior  end  where  it  passes  between  the  beginning  pallial 
hemispheres.  As  the  roof  plate  expands  further,  the  anterior  part  is  next 
thrown  into  longitudinal  folds.  The  ridge  forms  the  epithelial  lining  of  the 
tela  chorioidea  of  the  third  ventricle  (diatela).  By  further  growth  and  vas- 
cularization  of  its  mesodermal  covering  at  the  beginning  of  the  third  month, 
there  is  formed  the  chorioid  plexus  of  the  third  ventricle  (diaplexus).  Lateral 
extensions  of  the  tela  form  the  chorioid  plexuses  of  the  lateral  ventricles  (see 
p.  554).  In  the  fifth  week  a  protrusion  appears  at  the  caudal  end  of  the  median 
ridge  which  is  the  beginning  of  the  epiphysis.  Soon  after  this,  the  furrow  which 
forms  its  caudal  boundary  extends  forward  along  the  upper  part  of  the  sides  of 
the  walls,  marking  off  a  fold  which  is  the  lateral  continuation  of  the  median 
protrusion.  From  the  median  protrusion  is  later  formed  the  pineal  body, 
while  from  the  lateral  folds  are  formed  the  pineal  stalk,  and  in  front  the 
habenula,  with  its  contained  nucleus  (ganglion)  habenula,  and  the  stria 
medullaris.  Still  further  caudally,  the  anterior  part  of  the  mid-brain  forms 
a  horseshoe-shaped  fold  the  arms  of  which  extend  forward  over  the  dien- 
cephalon, ventral  to  the  pineal  folds.  The  median  part  of  this  fold  forms  the 
anterior  corpora  quadrigemina.  From  its  lateral  extensions  are  formed  the 
anterior  brachia  of  the  anterior  corpora  quadrigemina,  the  pulvinar  and  the 
lateral  and  medial  geniculate  bodies,  all  of  which  (pulvinar  ?)  later  receive  optic 
fibers.  The  transverse  furrow  which  forms  the  boundary  between  the  rudi- 
ments of  the  pineal  body  and  of  the  anterior  corpora  quadrigemina  marks  the 
location  of  the  future  posterior  commissure  (Figs.  464,  465  and  466) . 

The  part  of  the  roof  anterior  to  the  pineal  fold,  as  already  stated,  forms  the 
tela  chorioidea  of  the  third  ventricle.  Certain  folds  appear  in  it,  however, 
which  are  more  clearly  indicated  in  later  stages  of  embryonic  development 
than  in  the  adult  and  which  probably  represent  structures  already  mentioned 


THE   NERVOUS   SYSTEM. 


541 


as  common  to  the  vertebrate  brain  ("cushion"  of  the  epiphysis,  velum  trans- 
versum,  paraphysis?)    (p.  461  and  Fig.  402). 

From  the  above  it  is  evident'that  at  the  close  of  the  fifth  week  the  rudiments 
of  the  various  parts  of  the  diencephalon  are  already  well  marked.  These 
rudiments  are  principally  indicated  by  foldings  of  the  walls,  there  being  no  very 
strongly  marked  differences  of  thickness  except  the  early  differentiation  between 
the  median  and  lateral  plates.  From  this  time  on,  both  general  and  local 

Lamina  terminalis 


Cavity  of  ant.  olfact.  lobe 

Anterior  arcuate  fissure 

Cavity  of  post,  olfact.  lobe 

Chorioid  fold 

Hippocampal  fissure 


Lateral  geniculate  body 


Pineal  region 


Ant.  corp.  quad.  (ant.  colliculus) 
(extending  forward 
into  ant.  brachium) 


Angulus  praethalamicus 


(a)  (b) 
(c) 


Corpus  striatum 


Roof  plate  of  diencephalon 


FIG.  464. — Dorsal  view  of  a  model  of  the  hrain  of  a  13.6  mm.  human  embryo  (beginning  of  6th 
week).  The  dorsal  part  of  the  pallium  on  each  side  has  been  removed.  Compare  with 
Figs.  465  and  466.  His. 

thickenings  of  the  lateral  walls  occur.  This  indicates  a  rapid  proliferation 
of  the  cells,  especially  a  differentiation  of  the  nerve  cells  and  consequent  forma- 
tion of  masses  of  gray  and  white  matter.  Another  factor  affecting  the  dien- 
cephalon is  the  subsequent  growth  backward  over  it  of  the  cerebral 
hemispheres. 

During  the  second  month,  the  lateral  walls  become  thickened,  forming 
a  prominence  on  the  inner  surface  of  each  side.  This  reduces  much  of  the 
cavity  of  the  third  ventricle  to  a  cleft  and  in  the  third  or  fourth  month  a  fusion  of 


542 


TEXT-BOOK  OF  EMBRYOLOGY. 


a  portion  of  these  two  projections  takes  place,  forming  the  commissure,  mollis 
or  massa  intermedia.     The  condition  at  this  stage  is  shown  in  Fig.  467.     Later 


Ant.  corp.  quad.  Diencephalon 


Tegmental 
swelling 

Mammillary 
body 

Tuber 
cinereum 


Pallium 


Beginning  of 
fossa  Sy.vii 


'nt-  I   ol 
ostJ10 


Ifact. 
ibe 


Optic  stalk 


Infundibulum       Hypophyseal  pouch. 

FlG.  465. — Lateral  view  of  the  model  of  the  brain  of  a  13.6  mm.  human  embryo  (beginning  of  6th 
week).     F,  Beginning  of  frontal  lobe;   T,  beginning  of  temporal  lobe.     His. 

this  protrusion  thrusts  the  lateral  structures  above  described  (the  pulvinar, 
geniculate  bodies  and  brachia)  to  the  side,  the  cavity  of  the  lateral  geniculate 

Epltbalnmus  (Corpus  pineale)  Mclathalamus  (Corpora  geniculata) 


Rhinencephalon 

Corpus  striaturu' 
Sulcns  liypothalamicus     , 
,  Hypothalamu! 

Chiasma  opticum 


FlG.  466. — From  a  model  of  the  brain  of  a  13.6  mm.  human  embryo,  right  half, 
seen  from  the  left  side.     His,  Spalteholz. 

body  being  obliterated.     The  prominence  itself  extends  to  the  tegmental  swell- 
ing (see  Figs.  467-8)  and  there  thus  arises  the  possibility  of  direct  connections 


THE  NERVOUS  SYSTEM. 


543 


between  these  two  structures.     There  can,  then,  be  distinguished  in  thedien- 
cephalon  three  regions,  a  hypothalamic  region,  as  already  described,  an  epiihala- 


Hippocampal 
fissure 


Chorioid  fissure 
Angulus  praethalamicus 

Foramen  of  Mon: 

Ant.  arcuate  fissur 

Preterminal  area 

Ant.  olfact.  lobe 

Olfactory  nerve 

Post,  olfact.  lobe 


Hypothalamic  region 
Mammillary  region 


Lamina  terminalis 


R.o.        Hypophysis 


FIG 


.  467. — Median  sagittal  section  of  the  brain  of  a  75  weeks'  human  embryo.  Aq.  S.,  Aquasductus 
Sylvii;  C.  c.,  fold  between  mid- and  interbrain;  C.  m.,  commissura  mollis;  C.  s.,  corpus  stri- 
atum;  H.  b.,  tegmental  swelling;  R. g.,  geniculate  recess;  R.i.,  recessus  infundibuli;  R.o., 
recessus  (prae-?)  opticus;  S.  h.,  habenular  evagination;  5.  M.,  sulcus  hypothalamicus;  S.p., 
pineal  evagination;  T.  T.,  thalamus.  His. 


mic  region  comprising  the  pineal  body,  ganglia  habenulae  and  related  structures, 
and  finally  the  thalamus  proper.     In  the  latter,  the  geniculate  bodies  already 


Corpus  stnaiiin 


Epithalamus  (Corpus  pinealej 

Metathalainus 
(Corpora  geniculaia) 


Corpora  quadrixnui 


'••Pedunculus,  cejebri 


RhinencepUalon     /     .- 
Pars  optica  hypothalami     /' 
chinsiua  opticum'    .•' 
Hypophysis  ' 

Pars  maraillaris  bypothalami" 
Pens  [Varo 


••Cerebellum 
-.-Fossa  rhomboidea 


Medulla  oblongata 


FIG.  468. — Brain  of  a  human  foetus  in  the  3d  month,  right  half,  seen  from  the  left.     His,  Spalteholz. 


mentioned  constitute  a  metathalamic  portion,  while  the  portion  derived  from 
the  thickened  part,  which  is  continuous  anteriorly  with  the  corpus  striatum, 

35 


544 


TEXT-BOOK  OF  EMBRYOLOGY. 


differentiates  various  nuclei,  especially  those  which  receive  the  general  somatic 
sensory  fibers  (medial  lemniscus  or  fillet),  and  other  nuclei  in  relation  to  definite 
centers  of  the  pallium.  The  thalamus  is  thus  strongly  developed,  owing  to  its 
containing  the  nuclei  which  receive  the  general  sensory  (ventro-lateral  nuclei), 
acoustic  (medial  geniculate  bodies),  and  optic  (lateral  geniculate  bodies) 
systems  of  fibers  and  which  in  turn  send  fibers  (thalamic  radiations]  to  the  pallium. 
These  thalamic  nuclei  do  not  receive  fibers  probably  until  after  the  middle  of  the 
second  month.  About  this  time  the  thalamic  radiations  begin  to  be  formed 
from  the  thalamic  nuclei  and  grow  toward  the  corpus  striatum  which  they  reach 
toward  the  end  of  the  second  month.  With  the  first  appearance  of  the  cortical 


TbaJatniis 


Bbinencephalon 

Recessus  opticus 

Chiasma  Opticiim    ..• 


Recessua  infundibnli  '     / 
Infimdibulum 

Pedunculus  cerebri 


Velum  raedul- 
lare  anterius 


Pon,  [VaroM]  \M 

Ve 
FIG.  469.  —  Adult  human  brain,  right  half,  seen  from  the  left,  partly  schematic.     Spalteholz. 


V;ephalon\ 


layer  of  the  developing  neopallium  (see  p.  549)  they  penetrate  the  corpus  stria- 
tum and  pass  to  the  cortex,  forming  the  beginning  of  the  internal  capsule,  and 
corona  radiata.  It  has  already  been  pointed  out  (p.  474)  that  the  great  develop- 
ment of  the  thalamus  and  its  radiations  is  more  recent  phylogenetically  and  is 
due  to  the  newly  acquired  connections  with  the  neopallium. 

Before  the  development  of  these  neopallial  connections,  other  tracts  have 
begun  to  appear  which  represent  older  epithalamic  and  hypothalamic  connec- 
tions existing  practically  throughout  the  Vertebrates  (pp.  ^474  and  475).  Some 
of  the  hypothalamic  connections  are  the  mammillo-tegmental  fasciculus  which 
appears  early  in  the  second  month,  the  thalamomammillary  fasciculus 
(Vicq  d'Azyr's  bundle),  which  appears  later,  and  the  bundles  from  the  rhinen- 
cephalon  (p.  512)  and  archipallium  (columns  of  the  fornix,  middle  of  fourth 
month,  p.  558).  In  the  hypothalamic  region  is  also  differentiated  the  corpus 


THE   NERVOUS   SYSTEM. 


545 


Luysii,  connected  by  fiber  bundles  with  the  corpus  striatum  and  tegmentum. 
Epithalamic  connections  are  represented  by  bundles  from  anterior  olfactory 
regions  (stria  medullaris,  seventh  week) ,  by  the  commissura  habenularis,  and  by 
bundles  to  caudal  regions  (fasciculus  reiroflexus  of  Meynert  to  the  inter  pedun- 
cular ganglion,  middle  of  second  month),  (pp.  474  and  512.)  The  posterior 
commissure  fibers  are  formed  early  in  the  second  month  in  the  fold  between 
mid-  and  inter-brain  (Fig.  467).  (Fig.  470). 


St. 


01. 


FIG.  470.— Construction  of  the  brain  of  a  19  mm.  human  embryo  (7^  weeks),  showing  the  stage  of 
development  of  some  of  the  principal  fiber-systems.  His. 

C.c.,  posterior  commissure;  F.  s.,  tractus  solitarius;  F.t.,  fasciculus  spinalis  trigemini  (spinal  V); 
K,  nuclei  of  dorsa!  funiculi  of  cord;  L.,  medial  longitudinal  fasciculus;  M.,  fasciculus  retro- 
nexus  of  Meynert;  Ma.,  mammillary  bundle;  n.i.,  nervus  intermedius;  O.,  olive;  Ol.,  olfactory 
nerve;  S.,  fillet;  St.,  stria  medullaris  thalami;  T.,  thalamic  radiation;  T.  o.,  tractus  opticus; 
V,  Gasserian  ganglion;  VII,  facial  nerve  and  geniculate  ganglion;  VIII,  ganglia  of  acoustic 
nerve;  IX,  N.  glossopharyngeus;  X,  N.  vagus. 

The  Telencephalon  (Rhinencephalon,  Corpora  Striata  and  Pallium). 

To  understand  the  development  of  this  part  of  the  brain  it  is  necessary  to 
keep  firmly  in  mind  certain  relations  which  are  laid  down  at  a  comparatively 
early  stage.  Some  of  these  relations  are  shown  in  the  diagram  of  the  inner  sur- 
face of  a  model  of  a  brain  of  four  weeks.  At  this  stage  the  pallium  is  unpaired, 
i.e.,  there  is  no  median  furrow  separating  the  two  halves  of  the  pallial  expansion. 
The  various  boundaries  of  the  pallium  in  one  side  are  (i)  the  median  line  uniting 


546 


TEXT-BOOK  OF  EMBRYOLOGY 


the  two  halves  of  the  pallial  expansion  (Fig.  471,  be) ;  (2)  the  boundary  line  or 
line  of  union  with  the  thalamus  lying  caudally  (pallio-thalamic  boundary) 
(Fig.  471,  cd);  (3)  the  boundary  between  pallium  and  corpus  striatum  (strio- 
pallial  boundary)  (Fig.  471,  bd).  The  boundaries  of  the  future  corpus  striatum 
are  (i)  the  median  (Fig.  471,  ab),  (2)  the  strio-pallial  (Fig.  471,  bd),  (3)  the 
strio-thalamic  or  peduncular  (Fig.  471,  de)  and  (4)  the  strio-hypothalamic  (Fig. 
471,  ae).  The  internal  prominence  which  is  the  rudiment  of  the  corpus 
striatum,  has  three  limbs  or  crura,  (i)  a  ridge  proceeding  forward  (anterior 
crus),  which  corresponds  externally  to  the  furrow  (external  rhinal  furrow) 
forming  the  lateral  boundary  of  the  anterior  olfactory  lobe,  (2)  a  middle  crus 


Prosencephalon 
( Fore  •  bram) 


Rhincnceplialon1-- 
Corpus  striatum 

Pars  optica  liypothalami     • 

Pars  mamillaris  hypothalarui 

Pans  [Varolil 


f      T:       ^ 

MyelericephaJonl 
(After-brain)] 

'.                              I!  '  '// 

Pars  ventralis  -- 
Sulcus  lirnitans 

--{-• 

Corporn  quadrigemina 


9^....-----/-f^--  Peduuculus  cerebri 


Brachium  conjunctivi 

and  velum  niedullar 

auterius 


Rhomb- 

encephalon 

"  (Lozenge -shaped 
,brain) 

Cerebellum 


FIG.  471. — From  a  model  of  the  brain  of  a  human  embryo  at  the  end  of  the  first  month,  right 
half,  seen  from  the  left.     His,  Spalteholz. 

corresponding  to  the  constriction  separating  the  two  olfactory  lobes,  and  (3)  a 
posterior  crus  corresponding  to  the  posterior  boundary  of  the  posterior  olfactory 
lobe.  This  latter  is  merged  with  the  earlier  furrow  separating  the  telencephalon 
from  the  thalamus  and  hypothalamus  (peduncular  furrow).  What  may  be 
called  the  main  body  of  the  corpus  striatum,  from  which  these  limbs  radiate, 
soon  becomes  expressed  externally  by  a  shallow  depression  in  the  lateral  sur- 
face of  the  hemispheres  immediately  dorsal  to  the  olfactory  lobes.  This 
depression  is  the  first  indication  of  the  fossa  Sylvii  (Fig.  465). 

The  boundaries  of  the  pallial  hemisphere  above  indicated  are  identical 
with  the  boundaries  of  the  future  foramen  of  Monro. 

The  median  lamina  uniting  the  two  halves  of  the  pallium  and  the  two  corpora 
striata  may  be  termed  the  lamina  terminalis  and  represents  the  roof  plate  and 
floor  plate  of  this  region.  The  point  of  meeting  of  the  roof  plate  and  floor 


THE   NERVOUS   SYSTEM. 


547 


plate  at  the  end  of  the  tube  is  often  taken  to  be  at  the  recessus  neuroporicus ; 
and  the  lamina  terminalis  or  end  wall  of  the  neural  tube,  more  strictly  speaking, 
is  limited  to  the  median  wall  ventral  to  this  point.  Here  it  will  be  understood 
as  including  the  median  wall  to  the  point  where  the  pallio-thalamic  boundary 
begins,  marked  later  by  the  angulus  pr&thalamiciis  of  His  (see  p.  554  and  Fig. 
480). 

Rhinencephalon. — The  term  rhinencephalon  is  a  convenient  one  for 
those  basal  structures  of  the  fore-brain  which  are_in  most  intimate  connection 
with  the  olfactory  nerve.  The  term  has  been  extended  by  some  to  include 
the  pallial  olfactory  structures.  For  descriptive  purposes  it  is  here  used  in 
the  more  limited  sense. 

At  the  fourth  week,  as  already  indicated  (p.  546,  Fig.  472),  there  is  a  slight  longi- 
tudinal furrow  on  the  external  surface,  marking  the  ventral  limit  of  the  pallial 


FIG.  472. — Lateral  view  of  outside  of  brain  shown  in  Fig.  471.     His. 

eminence.  The  part  of  the  brain  ventral  to  this  furrow  is  the  rhinencephalon, 
Somewhat  later  the  latter  becomes  better  marked  off,  the  fissure  forming  its 
boundary  on  the  lateral  surface  being  the  external  rhinal  fissure  (Fig.  462). 
Later  the  mesial  side  is  also  marked  off  by  an  extension  of  the  fissure  around 
on  the  mesial  side  (medial  rhinal  fissure)  and  also  by  a  notch,  the  incisura 
prima,  a  continuation  of  which  later  ascends  along  the  middle  part  of  the 
median  surface  of  the  hemispheres  and  is  known  as  the  anterior  arcuate  fissure 
(jissura  prima  of  His).  (Fig.  480.)  The  existence  of  a  fissura  prima  in  early 
stages,  however,  is  doubtful.  At  about  this  time,  the  rhinencephalon  shows  a 
beginning  division  into  anterior  and  posterior  portions,  the  anterior  and  posterior 
olfactory  lobes,  the  whole  structure  assuming  a  bean-shape  (comp.  p.  549) 
(Fig.  465).  On  the  lateral  surface  immediately  above  this  constriction  is  the 
beginning  concavity  in  the  lateral  surface  of  the  hemispheres  which  marks  the 


548 


TEXT-BOOK  OF  EMBRYOLOGY. 


earliest  appearance  of  the  fossa  Sylvii.  The  external  rhinal  fissure,  as  it 
becomes  more  pronounced,  may  be  regarded  as  an  extension  forward  of  the 
fossa  (anterior  crus  of  the  corpus  striatum) .  On  the  mesial  surface  the  incisura 
prima  marks  this  constriction.  With  the  further  curvature  of  the  hemispheres, 
the  anterior  lobe  becomes  bent  back  under  the  posterior  (third  month),  but 
later  is  again  directed  forward.  It  contains  a  diverticulum  of  the  fore-brain 
cavity.  The  cavity  of  the  posterior  lobe  is  not  so  well  marked  off  and  is 
bounded  by  the  corpus  striatum  and  the  inward  projection  of  the  incisura 
prima.  (Figs.  462,  463,  465,  466  and  480.) 

The  olfactory  nerve  at  the  end  of  five  weeks  has  reached  the  anterior  lobe 
on  its  ventral  and  posterior  side.  The  lobe  develops  into  the  receptive  centers  for 
the  nerve — the  olfactory  bulb;  into  the  stalk  in  which  the  secondary  olfactory 


Gyrus  olfact.  medialis 

Gyrus  olfact.  medius 

Gyrus  diagonalis 


Cerebellum 


Insula 

Gyrus  olfact.  lat. 

Gyrus  ambiens 
Gyrus  semilunaris 

Olive 


FIG.  473. — Ventral  view  of  the  brain  of  human  foetus  at  the  beginning  of  the  4th  month.  Kollmann. 

tract  proceeds;  and  also  into  a  triangular  area  where  the  tract  divides — the 
trigonum.  The  posterior  olfactory  lobe  develops  into  the  anterior  perforated 
space  and  an  eminence  known  as  the  lobus  pyriformis  which  becomes  reduced 
later  (comp.  Fig.  408,  G  and  H).  From  it  is  developed  the  gyrus  olfactorius  later- 
alls,  connected  with  the  lateral  division  of  the  olfactory  tract  and  ihegyri  ambiens 
and  semilunaris  (Fig.  473).  On  the  mesial  wall,  the  posterior  lobe  is  especially 
connected  with  the  region  between  the  anterior  arcuate  fissure  and  the  lamina 
terminalis  (trapezoid  area  of  His,  parolfactory  or  preterminal  area  of  G.  Elliot 
Smith)  (Fig.  480).  Part  of  this  mesial  region  represents  the  anterior  portion 
of  the  archipallium  (comp.  Fig.  408,  G  and  H  and  p.  512). 

Corpora  Striata  and  Pallium. — The  leading  feature  of  the  development 
of  this  part  of  the  brain  is  the  great  expansion  of  the  pallial  hemispheres.  That 
part  of  the  brain  wall  marked  externally  by  the  fossa  Sylvii  and  internally  by  the 
body  of  the  corpus  striatum,  and  especially  that  part  where  the  corpus  striatum 


THE  NERVOUS   SYSTEM.  549 

is  continuous  with  the  thalamus  (peduncular  part) ,  may  be  considered  as  a  fixed 
point  from  which  the  pallial  walls  expand  in  all  directions,  anteriorly,  dorsally 
and  posteriorly,  i.e.,  in  both  transverse  and  longitudinal  directions.  At  first, 
this  expansion  causes  the  pallial  hemispheres  to  assume  a  bean-shape  with  the 
hilum  at  the  fixed  point  (Fig.  465).  The  anterior  end  curves  downward  and 
forms  the  frontal  lobe  with  its  enclosed  cavity  (anterior  horn  of  the  lateral  ven- 
tricle). The  posterior  end  curves  downward  caudally  and  forms  the  temporal 
lobe  with  the  descending  horn  of  the  lateral  ventricle.  At  the  same  time,  owing 
to  the  great  expansion  in  a  transverse  plane  of  each  pallial  eminence,  the 
median  lamina  uniting  them  (Figs.  463  and  464)  not  sharing  in  this  growth, 
there  are  formed  the  hemispheres  with  their  cavities,  the  lateral  ventricles,  and 
the  great  longitudinal  jissure  between  the  hemispheres.  Later,  vascular 
mesodermal  tissue  fills  this  fissure,  forming  the  falx  cerebri.  The  paired 
cavities  of  the  pallium  are  connected  with  the  unpaired  end-brain  cavity  (aula) 
by  the  foramina  of  Monro,  the  boundaries  of  which  are  the  same  as  those  of  the 
pallium  described  above  (p.  545). 

At  first  the  walls  of  the  telencephalon,  like  those  of  other  parts  of  the  tube, 
are  epithelial  in  character  and  nearly  uniform  in  thickness.  By  proliferation 
there  is  formed  a  several-layered  epithelium  differentiated  into  an  inner 
nuclear  layer  and  an  outer  marginal  layer.  Later  a  mantle  layer  is  differen- 
tiated. The  hemispheres  are  late  in  development  and  until  the  end  of  the 
second  month  the  walls  are  thin  and  simply  show  the  above  three  layers. 
Toward  the  end  of  the  first  month  a  greater  activity  in  cell  proliferation  takes 
place  in  the  basal  portion  -of  the  telencephalon  which  thickens  into  the  corpus 
striatum.  At  eight  weeks  there  first  appears  on  the  external  surface  of  the 
corpus  striatum,  a  cortical  layer  of  cells  lying  next  the  marginal  layer  and  sepa- 
rated from  the  inner  layer  by  an  intermediate  layer  comparatively  free  of  cells 
and  known  as  the  fibrous  or  medullary  layer  (see  p.  561).  The  differentiation 
thus  begun  extends  gradually  around  the  circumference  of  the  hemispheres 
until  the  mesial  surface  is  reached.  This  differentiation  permanently  ceases 
at  the  medial  pallial  margin.  The  cortical  layer  does  not  extend  as  far  as 
the  medullary  layer,  thus  leaving  an  uncovered  medullary  layer  on  the  mesial 
hemisphere  wall.  As  a  result  of  this,  there  is  in  this  region,  passing  toward 
the  median  line,  (i)  a  region  covered  with  a  cortical  layer  (limbus  corticalis 
of  His) ;  (2)  an  uncovered  medullary  layer  (limbus  medullaris);  (3)  a  fibrous 
transitional  zone  (the  tcenia)  passing  into  (4)  a  membranous  zone,  the  roof 
plate. 

This  process  resembles  that  taking  place  in  other  parts  of  the  neural  tube, 
in  which  there  is  the  same  progressive  development  from  the  ventral  portion 
of  the  lateral  wall  to  the  dorsal  border  of  the  same,  where  the  latter  passes  into 
the  roof  plate  which  is  either  ependymal  or  expanded  into  a  thin  membrane. 


550  TEXT-BOOK  OF  EMBRYOLOGY. 

The  longitudinal  growth  of  the  hemispheres  naturally  affects  the  form  of  a 
number  of  its  structures.  As  already  mentioned,  this  growth  consists  in  an 
elongation  around  a  fixed  point,  which  may  be  regarded  as  located  on  its  ven- 
tral border,  the  result  of  this  being  a  curving  down  in  front  and  behind  this 
point.  This  is  especially  marked  in  the  caudal  half  which  thereby  becomes 
curled  first  ventrally  and  then  forward,  thus  forming  a  spiral.  This  growth  in 
length  is  interstitial,  i.  e.,  due  to  expansion  of  the  intermediate  parts,  and  pari 
passu  with  it  there  is  an  elongation  not  only  of  the  corpus  striatum  and 
structures  in  the  mesial  hemisphere  wall  (hippocampal  formation,  corpus  callo- 
sum,  chorioid  plexus  of  lateral  ventricle),  but  also  of  adjacent  thalamic  struc- 
tures (stria  terminalis  or  semicircularis) ,  as  described  later. 


FIG.  474. — View  of  the  inside  of  the  lateral  wall  of  anterior  part  of  fore-brain.     Human  embryo 

of  about  4!  weeks.     His. 

C,  Corpus  striatum;  H,  pallium;  h.  R,  posterior  olfactory  lobe;  L,  lamina  terminalis:  O,  re- 
cessus  (prae-?)  opticus;  R.  i.,  recessus  infundibuli;  5.  M..  sulcus  hypothalamicus;  St,  hypo- 
thalamus;  T,  thalamus;  v.  R.,  anterior  olfactory  lobe. 

The  early  divisions  of  the  corpus  striatum  have  been  mentioned,  and  also 
the  relations  of  its  parts  with  the  rhinencephalon.  The  anterior  end  of  the 
corpus  striatum  at  this  period  and  later  shows  a  longitudinal  division  into 
three  portions,  a  lateral,  a  middle  and  a  medial,  due  to  the  original  division 
into  three  limbs  described  above  (p.  545).  (Figs.  474,  475,  and  476.)  With 
the  elongation  backward  of  the  hemisphere  the  corpus  striatum  also  becomes 
elongated,  being  drawn  out  and  curled  around  the  peduncle  or  stalk  'of  the 
hemisphere  and  forming  a  thickening  along  the  elongated  wall.  This  caudal 
prolongation  of  the  striatum  is  its  cauda  (tail]  and  extends  to  the  tip  of  the  in- 
ferior horn  (Figs.  475  and  476).  The  medial  portion  of  the  corpus  striatum 
forms  a  triangular  projection  (Figs.  464  and  466)  the  edge  of  which  is  directed 
toward  the  foramen  of  Monro. 


THE  NERVOUS  SYSTEM. 


551 


The   stalk   of   the  hemisphere  has  already  been  mentioned  as  including 
that  part  where  corpus  striatum  and  thalamus  meet.     In  this  region,  according 


v.m. 


FIG.  475. — View  of  inside  of  the  lateral  wall  of  lateral  ventricle  of  a  human  foetus  at  beginning 

of  third  month.     His. 

Bb,  bulbus  olfactorius;  C./.,  lateral  limb  of  corpus  striatum;  C.m.,  medial  segment  (consisting  of 
the  middle  and  inner  limbs)  of  the  corpus  striatum.  The  furrow  between  these  two  parts 
opens  into  the  anterior  olfactory  lobe;  hRl.,  posterior  olfactory  lobe;  L.f.,  frontal  lobe;  L.o., 
occipital  lobe;  Og.,  olfactory  nerve;  R.  z.,  recessus  infunclibuli;  R.  o.,  recessus  (prae-?)  opticus; 
St.,  stalk  of  hemisphere  (strio-thalamic  junction);  V.I.,  lateral  ventricle;  v.Rl.+Bb,  anterior 
olfactory  lobe. 

to  some,  there  is  a,  fusion  of  the  striatum,  the  medial  wall  of  the  hemisphere  and 
the  anterior  part  of  the  thalamus.     According  to  others,  the  increase  in  bulk  of 


Medial  wall 


Chorioid  plexus  of 
lateral  ventricle 


Lamina  terminalis 

Taenia  thalami 
Thalamus 

Habenula 

Trigonum  subpineale 
Cerebellum 


Myelencephalon 


Lateral  ventricle 
!audate  nucleus  (head) 

•Medial  wall 

•Caudate  nucleus  (tail) 

Pineal  body 

Median  sulcus 


Mesencephalon 
Fourth  ventricle 


~^™^^^ 

FIG.  476. — Dorsal  view  of  the  brain  of  a  3  months'  (45  mm.)  human  foetus.    The  dorsal  part  of  each 
cerebral  hemisphere  has  been  removed.     Kollmann. 

this  region  is  produced  by  a  simple  thickening  of  the  walls,  thus  causing  a  flat- 
tening out  or  shallowing  of  the  grooves  marking  the  junctions  of  striatum  and 


TEXT-BOOK  OF  EMBRYOLOGY. 


FIG.  477. — i,  2  and  3,  Schematic  horizontal  sections  through  human  embryonic  fore-brains  at  dif- 
ferent stages  of  development;  4,  vertical  section  through  fore-brain  at  about  same  stage  as  i. 
Goldstein. 

a,  That  part  of  the  lateral  ventricle  lying  between  the  corpus  striatum  and  the  junction  of  medial 
hemisphere  wall  and  thalamus  (leading  into  the  inferior  horn);  b,  furrow  or  trough  between 
mesial  hemisphere  wall  and  thalamus,  produced  by  backward  extension  of  hemisphere;  c.  i., 
internal  capsule;  F.  M.,  foramen  of  Monro;  h,  external  surface  at  junction  of  mesial  hemi- 
sphere wall  and  thalamus;  Str.,  corpus  striatum;  Th.,  thalamus;  U,  place  where  mesial  hemi- 
sphere wall  continues  into  the  thalamus  wall  (junction  of  hemisphere  wall  and  thalamus) ; 
U1,  place  where  mesial  hemisphere  wall  is  continuous  with  lateral  hemisphere  wall. 

In  i,  owing  to  the  thickening  of  U  and  growth  of  the  corpus  striatum,  these  two  are  brought 
into  apposition,  as  indicated  by  the  dotted  lines  on  the  right,  and  apparently  fuse,  obliterating 
a  and  producing  the  condition  shown  in  2  and  3.  In  2  and  3  the  position  of  the  former 
space  a  is  indicated  by  the  dotted  lines  a — a'  By  comparison  with  4,  it  will  be  seen  that  this 
obliteration  by  apparent  fusion  is  actually  produced  by  a  filling  up  from  the  bottom  of  a  (in- 
dicated faintly  by  dotted  lines  on  the  right  in  4).  The  thickening  of  the  walls  at  this  region 
also  produces  a  shallowing  of  b  (indicated  by  dotted  lines  on  the  right  in  i).  The  principal 
cause  of  this  general  thickening  is  the  passage  of  the  fibers  of  the  thalamic  radiation  to  the 
hemispheres  and,  later,  of  fibers  from  hemisphere  to  pes,  forming  the  internal  capsule  (4,  2 
and  3). 


THE   NERVOUS   SYSTEM. 


553 


thalamus  on  the  ventricular  surface,  and  between  medial  hemisphere  wall  and 
thalamus  externally  (Fig.  477).  The  effect  is  much  the  same  whether  accom 
plished  by  apposition  and  fusion  or  by  interstitial  thickening,  massive  con- 
nections being  formed  which  consist  mainly  of  fibers  connecting  hemispheres 
and  thalamus,  the  foramen  of  Monro  at  the  same  time  being  changed  in  form 
to  a  slit.  From  the  metathalamic  region  the  fibers  of  the  optic  and  acoustic 
pathways  grow  forward  into  the  hemispheres  (see  also  p.  544),  entering  more 
caudally  and  forming  the  retro-  and  sublenticular  portions  of  the  internal  ca'psule 
(comp.  p.  544).  That  part  of  the  thalamic  radiation  from  the  anterior  portion 
of  the  thalamus  (fillet  pathway)  also  forms  a  part  of  the  internal  capsule  as 
described  on  p.  544.  Later,  the  internal  capsule  is  completed  by  the  growth 


Medial  wall  • 


Caudate  nucleus  ' 

Internal  capsule  - 

Lentiform  nucleus  - 

Lateral  wall  • 


Chiasma 
Recessus  infundibuli 


^  -^ —  — _~ 


Chorioid  fissure 
Mesencephalon 

Pedunculus  cerebri 

Cerebellum 

Myelencephakm 


FIG.  478. — Lateral  view  of  the  brain  of  a  3  months'  (42  mm.)  human  foetus.     The  lateral  wall  of 
the  left  cerebral  hemisphere  has  been  removed.     His,  Kullmann. 

from  the  pallium  of  descending  fibers  from  the  neopallial  cortex,  through 
the  striatum  to  the  pes.  By  these  various  traversing  fibers  the  striatum  is 
divided  into  the  nucleus  lenticularis  or  lentiformis  and  the  nucleus  caudalus. 
The  posterior  arm  of  the  internal  capsule  is  formed  by  fibers  passing  between 
and  thus  separating  thalamus  and  lenticularis  (Figs.  477  and  478). 


THE  ARCHIPALLIUM. 

During  the  fifth  week,  following  the  stage  shown  in  Figs.  471  and  472, 
the  pallial  evaginations  or  hemispheres  have  become  much  more  pronounced 
and  consequently  the  foramina  of  Monro  much  better  defined.  A  comparison 
will  show  that  the  boundaries  of  the  foramen  of  Monro  are  essentially  unaltered. 
Anteriorly  it  is  bounded  by  the  medial  wall  connecting  the  two  hemispheres, 
posteriorly  by  the  boundary  between  pallium  and  thalamus,  ventrally  by  the 
corpus  striatum  and  junction  of  it  and  thalamus  (Figs.  463  and  479). 


554 


TEXT-BOOK  OF  EMBRYOLOGY. 


At  the  beginning  of  the  sixth  week  the  foramen  of  Monro  has  changed  some- 
what in  shape.  The  pallio-thalamic  part  of  its  boundary  passes  forward  and 
forms  the  above-mentioned  (p.  547)  acute  angle  (angulus  prasthalamicus)  with 
that  part  of  the  wall  uniting  the  two  hemispheres  (lamina  terminalis).  The 
latter  wall  descends  to  the  region  of  the  optic  recess.  The  inferior  part  of  the 
foramen  is  partly  closed  by  the  medial  part  of  the  corpus  striatum  as  already 
described.  (Comp.  Figs.  479,  464  and  466.)  In  the  ependymal  mesial  wall 
of  the  hemispheres  just  below  the  tagnia,  described  above,  there  arises  a  folding 
inward,  which  begins  anteriorly  near  the  angulus  praethalamicus  and  proceeds 
caudally  along  the  upper  (pallio-thalamic)  border  of  the  foramen  of  Monro. 
This  infolding  is  the  chorioid fissure.  In  the  ependymal  mesial  wall  there  are 


Pallium 


Foramen  of  Monro 
Corpus  striatum 


Eye 


III  ventricle 
Chorioid  fissure 

Mesodermal  tissue, 
forming  later  the 
chorioid  plexus. 


Pharynx 


Tongue 


FIG.  479. — Transverse  section  through  fore-brain  of  a  i6mm.  embryo  (six  to  seven  weeks).     His. 

now  the  following:  limbus  chorioideus  (the  infolded  part)  and  a  small  strip  of  the 
ependyma  wall  below  the  fold,  the  lamina  infrachorioidea  (Fig.  480).  This 
invagination  soon  becomes  very  deep,  resulting  in  the  formation  of  a  double- 
layered  ependymal  fold  (the  chorioid  fold,  plica  chorioidea)  lying  in  the  lateral 
ventricle  over  the  corpus  striatum  (Figs.  479,  464  and  482).  Later,  vascular 
mesodermal  tissue  passes  in  from  the  falx  between  the  lips  of  this  fold  and 
thereby  forms  the  chorioid  plexus  of  the  lateral  ventricles.  The  chorioid  fissure 
is  at  first  quite  short,  but  becomes  elongated  (Fig.  481)  with  the  above-described 
posterior  elongation  of  the  hemisphere  of  which  it  is  a  part,  and  thus  extends 
into  the  inferior  horn  of  the  temporal  lobe.  (Figs.  481  and  482.) 

Toward  the  end  of  the  second  month,  according  to  some  authorities  (His), 
but  not  until  considerably  later,  according  to  others  (Hochstetter,  Goldstein), 
another  furrow  appears  in  the  limbus  corticalis  above  and  parallel  to  the  chori- 


THE   NERVOUS  SYSTEM.  555 

oid  fissure,  and  known  as  the  posterior  arcuate  fissure.  This  fissure  does  not 
extend  at  first  as  far  forward  as  the  chorioid,  but  extends  farther  caudally, 
arching  downward  in  the  temporal  lobe  around  the  caudal  end  of  the  chorioid 
fissure  (Fig.  481).  The  posterior  arcuate  fissure  is  a  total  fissure,  involving  the 
wrhole  wall  and  producing  a  fold  on  the  inner  surface  of  the  medial  hemisphere 
wall  (plica  arcuata}.  The  temporal  or  caudal  part  of  this  whole  formation 
persists  in  the  adult  without  much  further  change.  The  fissure  here  becomes 
the  hippocampal  fissure  separating  the  fascia  dentata  from  the  gyrus  hippocam- 
pus; the  part  rolled  in  by  the  hippocampal  fissure  produces  the  eminence  in 
the  lateral  ventricle  known  as  the  cornu  ammonis  or  hippocampus  major; 


Frhl'' 


vRh    Vmr  Fstr  hRh 

FIG.  480. — Diagram  of  a  graphic  reconstruction  of  the  mesial  hemisphere  wall  of  a  16  mm.  human 
embryo  (about  six  weeks).  His,  Ziehen.  Cavities  are  dotted,  cut  surfaces  are  lined. 

Apt,  Angulus  praethalamicus;  Atr,  preterminal  area;  Fpr,  anterior  arcuate  fissure  (fissura  prima); 
Frhl,  mesial  termination  of  lateral  rhinal  fissure;  hRh,  posterior  olfactory  lobe  (tuberculum 
olfactorium  +  substantia  perforata  anterior) ;  Lt,  lamina  terminalis  (lined);  Vmr,  depression 
between  the  two  olfactory  lobes;  vRh,  anterior  olfactory  lobe  (bulbus  olfactorius  +  tractus 
olfactorius  +  trigonum  olfactorium). 

the  edge  of  the  limbus  corticalis  forms  the  fascia  dentata;  the  limbus  medullaris 
or  exposed  fibrous  part  is  ihefimbria  which  is  continued  by  its  thinning  edge 
or  tcenia  fimbrice  into  the  ependymal  or  epithelial  portion  (lamina  chorioidea) 
of  the  chorioid  plexus  of  the  lateral  ventricle.  The  chorioid  plexus  is  attached 
by  the  taenia  chorioidea  and  lamina  infrachorioidea  (here  the  lamina  affixa)  to 
the  brain  wall,  usually  near  the  junction  of  corpus  striatum  and  thalamus, 
thereby  forming  a  part  of  the  wall  of  the  inferior  horn  of  the  lateral  ventricle. 
At  this  line  of  junction  of  thalamus  and  hemisphere  wall  is  formed  the  stria 
terminalis.  The  fimbria  is  continuous  anteriorly  with  the  posterior  pillar  of 
the  fornix.  (Fig.  482.) 

The  anterior  part  of  the  hippocampal  formation  above  described  undergoes 


556 


TEXT-BOOK  OF  EMBRYOLOGY. 


Corpus  callosum  Hippocampal  fissure 


Olfactory  stalk 


Lamina  terminalis     | 

Anterior  commissure    | 

ginning  anterior  column  of  fornix 


I     Hippocampal  fissure 
Chorioid  fissure 


FIG.  481. — Graphic  reconstruction  of  the  mesial  hemisphere  wall  of  a  human  fcetus 

(fourth  month).     His,  from  Quain's  Anatomy. 

c  and  -v,  Anterior  and  posterior  parts  of  preterminal  area;  li,  lamina  infrachorioidea;  Icm,  limbus  or 
border  of  mesial  hemisphere  wall  (gyrus  dentatus  and  fimbria)  between  hippocampal  and 
chorioid  fissures;  P,  "stalk"  of  hemisphere. 


falx 


FIG.  482 — Diagram  of  a  transverse  section  through  the  fore-brain  of  a  human  foetus  (fourth 
month)  to  show  the  relations  of  the  margins  of  the  mesial  walls  of  the  hemispheres.  His, 
from  Quain's  Anatomy. 

Cs.,  corpus  striatum;  fi.,  limbus  medullaris  (fimbria);  fa.,  limbus  corticalis  (gyrus  dentatus);  h.f., 
hippocampal  fissure;  Th.,  thalamus 


THE  NERVOUS   SYSTEM. 


557 


further  modifications,  due  principally  to  the  development  of  commissural  fibers 
in  this  region.  Some  of  these  commissural  fibers  connect  the  representatives 
on  each  side  of  the  hippocampus  (limbus  corticalis)  of  this  region,  formino-  the 
fornix  commissure,  but  most  of  them  (corpus  callosum)  connect  the  rest  of  the 
cortical  areas  (neopallial  areas)  of  the  two  hemispheres. 

There  are  two  views  regarding  the  formation  of  these  commissures.  Ac- 
cording to  one  view,  the  first  commissural  fibers  appear  in  the  upper  (dorsal) 
part  of  the  lamina  terminalis.  The  latter  subsequently  expands  part  passu 

Corpus  callosum      Callosal  (continuation  of  hippocampal)  fissure 
Fornix  (continuation  of  fimbria)     ' 


Olfactory  stalk  I 

Optic  commissure  (chiasma) 


Lamina  terminalis  | 
Anterior  commissure 

Uncus 


ippocampal  fissure 


FIG.  483. — Graphic  reconstruction  of  the  mesial  hemisphere  wall  of  a  120  mm.  foetus  (end  of  four 

months).     His,  from  Quain's  Anatomy. 
b,  Fimbria;  cs  ,  cavity  of  septum  pellucidum  ("fifth"  ventricle,  ventricle  of  Verga);  km,  limbus 

corticalis  (gyrus  dentatus);  P,  stalk  of  hemisphere;  v,  outline  of  cavity  of  hemisphere  (lateral 

ventricle). 

with  the  expansion  of  the  corpus  callosum.  The  commissural  fibers  are  thus 
confined  to  the  original  walls  connecting  the  two  hemispheres.  According  to 
the  other  view,  there  is  a  secondary  fusion  of  the  mesial  hemisphere  walls  and 
in  these  fusions  the  fibers  cross.  The  first  fibers  appear  during  the  third  month 
and  form  at  first  a  small  band  in  the  upper  part  of  the  lamina  terminalis  (Fig. 
481).  These  fibers  come  partly  from  the  limbus  corticalis  (fornix  commissural 
fibers)  and  partly  from  other  parts  of  the  cortex  (callosal  fibers),  in  either  case 
traveling  along  the  intermediate  layer.  According  to  the  fusion  view,  the 
exposed  intermediate  layers  (limbi  medullares)  fuse  where  the  fibers  cross. 
This  fusion  can  easily  be  imagined  by  conceiving  the  opposite  surfaces  in 


558 


TEXT-BOOK  OF  EMBRYOLOGY.- 


question  to  be  brought  together  in  the  upper  part  of  Fig.  482.  It  is  more  prob- 
able, though,  that  not  only  the  first  fibers  cross  in  the  lamina  terminalis,  but 
that  the  later  ones  also  cross  in  extensions  of  the  latter.  There  are  three  views 
regarding  the  further  development  of  the  corpus  callosum.  The  first  is  that 
all  parts  are  represented  at  this  stage,  future  growth  being  by  intussusception  of 
fibers ;  the  second  is  that  the  part  first  formed  represents  the  genu,  the  rest  being 
added  caudally;  the  third  (His)  is  that  this  first  formed  part  represents  the 
middle  portion  of  the  callosum,  both  anterior  (genu  and  rostrum)  and  posterior 
(splenium)  portions  being  subsequently  added  (Figs.  481  and  483).  This 
latter  view  is  indicated  in  Fig.  483,  the  later  additions  being  shaded  darker. 

As  the  callosal  fibers  connect  the  limbi  medullares,  the  limbus  corticalis 
and  the  arcuate  fissure,  corresponding  to  the  gyrus  dentatus  and  hippocampal 
fissure  of  the  temporal  lobe,  lie  dorsal  to  the  callosum.  The  limbus  corticalis 
is  reduced  to  a  mere  vestige  (indusium  griseum  and  strice  Lancisi)  on  the 
dorsal  surface  of  the  corpus  callosum  the  fissure  becoming  the  callosal  fissure. 
The  part  of  the  limbus  medullaris  ventral  to  the  corpus  callosum,  corre- 
sponding to  the  fimbria  of  the  temporal  lobe,  forms  the  posterior  pillars  and 
body  of  the  fornix. 

These  relations  are  shown  in  the  following  table  from  His  (slightly  modi- 
fied): 


Upper  callosal  region 


Hippocampal  region 


Upper  lip  of  arcuate 

Gyrus  cinguli 

Gyrus  hippocampi 

fissure 

Arcuate  fissure              Fissura  corporis   cal-;  Fissura  hippocampi 

Limbus  Corticalis 

losi 

Cortical  layer  of  low- 

Cortical   covering  of    Gvrus  dentatus 

er  lip    of    arcuate 

callosum  (indusium 

fissure 

griseum   and  striae 

Lancisi) 

f 
Limbus  Medullaris  < 

Medullary     part     of 
lower  lip 

Callosum  and  fornix 

Fimbria 

Tasnia 

Tasnia  fornicis 

Taenia  fimbria? 

Lamina  chorioidea 

Plica  chorioidea 

Plica  chorioidea 

Lamina      infrachorio- 

Lamina  affixa 

Taenia  chorioidea 

idea 

Fibers  from  the  hippocampus  enter  the  fimbria  and  pass  forward  in  the  pos- 
terior pillars  and  body  of  the  fornix.  In  or  near  the  lamina  terminalis  these 
fibers  of  the  fornix  descend,  forming  the  anterior  pillars  of  the  fornix,  and  thence 
pass  back  of  the  anterior  commissure  and  caudally  to  the  mammillary  region. 


THE   NERVOUS   SYSTEM.  559 

They  are  joined  by  fibers  from  the  dorsal  surface  of  the  callosum  (fornix 
Itmgus),  i.e.,  from  the  vestigial  hippocampal  formation,  many  of  which  also 
descend  in  front  of  the  anterior  commissure  to  the  rhinencephalon.  The  trian- 
gular mesial  area  (septum  pellucidum)  included  between  callosum  and  fornix 
probably  represents  an  extended  part  of  the  lamina  terminalis  or  "commis- 
sure-bed," in  which  a  cavity  is  formed,  the  so-called////?,  ventricle  and  ventricle 
of  Verga.  A  remnant  of  the  hippocampal  formation  at  the  anterior  end  of 
the  callosum  is  represented  by  the  gyms  subcallosus  (Fig.  483). 

THE  NEOPALLIUM. 

The  hippocampal  or  cornu  ammonis  formation  and  preterminal  area 
represent  the  older  part  of  the  pallium  (archipallium)  comp.  pp.  475  and  476. 
This  part  of  the  pallium  is  olfactory  in  character,  being  mainly  a  higher  center 
for  the  reception  of  secondary  and  tertiary  olfactory  tracts.  In  its  extension 
backward  and  partial  obliteration  by  the  corpus  callosum,  its  embryologic 
presents  a  striking  similarity  to  its  phylogenetic  development  (compare  p.  475.) 
The  rest  of  the  pallial  hemispheres  (neopallium)  are  occupied  by  the  non- 
olfactory  higher  centers. 

The  further  growth  of  the  neopallial  hemispheres  leads  to  their  extension 
backward,  overlapping  the  caudal  portions  of  the  brain  tube.  In  the  course 
of  this  extension  the  occipital  lobe  and  its  cavity,  the  posterior  horn  of  the  lateral 
ventricle,  are  formed.  The  growth  of  various  portions  of  the  hemisphere  sur- 
face is  unequal,  producing  folds  (convolutions)  and  fissures.  This  folding 
may  be  partly  due  to  growth  in  a  confined  space,  but  especially  important  is 
the  relation  between  gray  and  white  matter.  The  gray  matter,  containing  not 
only  fibers  but  also  neurone  bodies,  remains  spread  out  in  a  comparatively  thin 
layer,  probably  to  accommodate  associative  connections.  The  white  matter,  on 
the  other  hand,  increases  in  thickness.  This  leads  to  a  folding  of  the  outer 
layer.  The  position  of  these  folds  is  probably  partly  determined  by  the  local " 
histological  differentiation  and  growth  of  various  cortical  areas  (p.  564). 
Only  some  of  the  earliest  and  most  important  of  these  folds  will  be  mentioned 
here. 

It  has  been  seen  (p.  546)  that  early  in  the  development  of  the  pallium  a 
shallow  depression  appears  on  the  external  lateral  surface  of  each  hemisphere, 
the  fossa  Sylvii  (Fig.  484).  The  bottom  of  this  is  the  future  insula.  It  is  ex- 
ternal to  the  corpus  striatum  and  does  not  grow  as  rapidly  as  the  parts  bound- 
ing it,  which  consequently  overlap  it,  forming  its  opercula.  These  bounding 
walls  are  formed  by  the  fronto-parietal  lobe  on  its  upper  side,  by  the  temporal 
on  its  lower,  and  by  the  orbital  on  its  anterior.  The  temporal  and  fronto- 
parietal  opercula  begin  about  the  end  of  the  fifth  month,  the  temporal  at  first 
36 


560 


TEXT-BOOK  OF  EMBRYOLOGY. 


growing  more  rapidly  but  later  the  fronto-parietal,  thereby  changing  the 
direction  of  the  Sylvian  fissure  from  an  oblique  to  the  more  horizontal  angle 
characteristic  of  man  as  compared  with  the  ape.  In  the  meanwhile  the 
development  of  the  frontal  lobe  leads  to  its  also  overlapping  the  insula.  If  the 


Parietal  lobe 


Occioital  lobe 


Mesencephalon 
Cerebellum 


Bulbus  olfactorius 


Gyrus  olfactor.  lat. 

Gyrus  semilunaris 
Gyrus  ambiens 


FIG.  484. — Lateral  view  of  the  brain  of  a  human  foetus  at  the  beginning  of  the 
4th  month.     Kollmann. 

frontal  lobe  fully  develops,  it  forms  a  U-shaped  operculum  between  the  fronto- 
parietal  and  the  orbital,  if  it  does  not  so  fully  develop  it  forms  a  V-shaped 
operculum,  and  a  still  less  developed  condition  is  shown  by  a  Y-shaped  arrange- 
ment in  which  the  frontal  lobe  does  not  completely  separate  the  fronto-parietal 

Sulcus  corp.  callosi 
Corpus  callosum  |          Splenium 

Gyrus  cinguli  |  |         |  Fissura  parieto-occip. 


Cavum  septi  pellucidi 

Lamina  rostralis 

Area  parolfactoria 

(praeterminalis) 


—  Cuneus 


KB—  Fissura  calcarina 


Fiss.  rhinica 
Lob.  temp. 

FIG.  485, — Median  view  of  the  left  half  of  the  brain  of  a  human  foetus  at  the  end 
of  the  yth  month.     Kollmann. 

and  orbital  opercula.  The  opercula  cover  the  fore-part  of  the  Sylvian  fossa 
during  the  first  year.  Conditions  of  arrested  development  are  thus  indicated  by 
the  Y-shaped  anterior  ascending  branch  of  the  Sylvian  fissure  coupled  with  an 
absence  of  the  pars  triangularis  and  also  by  a  partial  exposure  of  the  island 


THE  NERVOUS   SYSTEM. 


561 


of  Reil.  In  the  ape  the  frontal  operculum  is  absent  and  the  island  of  Reil 
partly  exposed. 

Toward  the  end  of  the  third  month  the  calcarine  fissure  appears,  producing 
on  the  ventricular  surface  the  eminence  known  as  the  calcar  avis.  At  the 
beginning  of  the  fourth  month  the  parieto-occipital  fissure  unites  with  it  forming 
the  cuneus.  The  parieto-occipital  reaches  the  superior  border  of  the  hemi- 
spheres by  the  sixth  or  seventh  month.  At  the  sixth  month  the  fissure  of  Rolando 
(central  fissure)  appears.  The  condition  of  the  surface  of  the  hemisphere  at 
the  end  of  the  seventh  month  is  shown  in  Figs.  485  to  488. 

The  early  histogenetic  development  of  the  pallial  wall,  resulting  in  the  dif- 
ferentiation into  the  usual  ependymal,  mantle  and  marginal  layers,  has  been 
mentioned.  (Fig.  489).  The  next  stage,  already  alluded  to  (p.  549),  marks  a 


Gyrus  front,  med. 
Gyrus  front,  inf. 
Gyrus  front,  sup.  — 
Gyrus     praecent.  — 

Gyrus  cent.  post. 
Lobulus  par.  sup. 
Lobulus  par.  inf. 

Lobus  occipitalis 


_  Sulcus  front,  sup. 
—  Sulcus  front,  inf. 
_  Sulcus  prascentralis 

_  Sulcus  centralis 
Sulcus  postcentralis 

Sulcus  interparietalis 
_    Fissura  parieto-occipit. 


FIG.  486. — Dorsal  view  of  the  cerebral  hemispheres  of  a  human  foetus  at  the  end 
of  the  7th  month.     Kollmann. 

difference  in  development  between  the  pallium,  as  well  as  other  supraseg- 
mental  structures,  and  the  rest  of  the  walls  of  the  neural  tube.  This  stage 
consists  apparently  in  a  further  migration  outward  of  the  neuroblasts  and  their 
accumulation  under  the  marginal  layer,  forming,  at  eight  weeks,  a  definite 
layer  of  closely  packed  cells,  the  beginning  of  the  cortex  (Fig.  490).  Later 
neuroblast  migrations  probably  add  to  this  layer.  It  has  already  been  men- 
tioned that  the  fibers  of  the  thalamic  radiation  appear  in  the  pallial  walls  about 
this  time.  They  proceed  internally  to  the  cortical  layer  and  thus  mark  the 
beginning  of  the  fiber  layer  (medullary  layer}  which  by  later  myelination 
becomes  the  white  matter  of  the  hemispheres. 

The  extension  of  the  process  of  differentiation  of  the  cortical  layer  from  the 
region  of  the  corpus  striatum  over  the  rest  of  the  pallium  has  also  been  men- 
tioned (p.  549).  It  is  probable  that  the  afferent  pallial  fibers  (thalamic  radia- 
tion) in  their  growth  keep  pace  with  this  process.  Those  fibers  from  the  lateral 


562  TEXT-BOOK  OF  EMBRYOLOGY. 

geniculate  bodies  proceed  to  the  occipital  region,  those  from  the  medial  genicu- 
late  bodies  to  the  temporal,  and  those  from  the  ventro-lateral  thalamic  nuclei 
(continuation  of  the  medial  fillet)  to  the  future  postcentral  region.  The 
afferent  pallial  fibers  are  often  termed  the  afferent  or  ascending  projection  fibers. 


Sulcus  oostcentralis  Sulcus  centralis 


Lobus  parietal,  sup.  . 

Region  cf  gyrus  sup-  J — '-^^  •« Sulcus  front,  inf. 

ramarg.  and  angular   «- 

Ramus  post.  ~  . 

.  Ramus  ant.  asc. 

-Fissura  Sylvii 
Sulcus  tempor.  med.    ^^^^^ 

Lobus  temporalis 

Gyrus  temp.  sup.        Gyrus  temp.  med. 

FIG.  487. — Lateral  view  of  the  right  cerebral  hemisphere  of  a  human  foetus  at  the  end 
of  the  7th  month.     Kolimann. 

The  axones  of  the  neuroblasts  of  the  cortical  layer  grow  inward,  entering  the 
medullary  layer.  Their  peripherally  directed  processes  become  the  apical 
dendrites  of  the  pyramid  cells  into  which  most  of  the  cortical  cells  differentiate. 
According  to  Mall  and  Paton,  this  change  of  direction  in  the  growth  of  the  axone 
is  due  to  a  turning  of  the  cell  axis  during  its  outward  migration.  It  would  seem 


Sulcus  orbitalis- 

^^B*          f       a    v    •  K  j«i 

Sulcus  olfactorius 

Insula       "^ —  Lobus  olfactorius 
Gyrus  olf.  lat.  — • 

Gyrus  semilun.  — 

Gyrus  ambiens 
Pyramid 
Medulla 


Post,  pole  of  cerebrum 


FIG.  488. — Ventral  view  of  the  brain  of  a  human  fetus  at  the  beginning 
of  the  sixth  month.     Ret-zius,  Kolimann. 

more  probable  that  the  cells  retain  an  original  bipolar  character  and  that  the 
inner  processes  differentiate  into  axones  instead  of  the  cells  going  through  a 
monopolar  stage  (pp.  491  and  492  and  Figs.  424  and  425).  The  axones  of  the 
cortical  cells  form  either  efferent  or  descending  projection  fibers,  proceeding  to 


THE  NERVOUS   SYSTEM. 


563 


other  parts  of  the  nervous  system,  or  crossed  (callosal)  and  uncrossed  association 
fibers,  connecting  various  cortical  areas  of  the  hemispheres.  The  basilar 
dendritic  processes  of  the  pyramid  cells  and  the  axone  collaterals  develop  last. 
Many  details  of  development  of  the  cells  in  Mammals  are  not  completed  until 
after  birth  (Fig.  491). 


FIG.  489. 


FIG.  490 


FIG.  489. — Section  through  the  pallial  wall  of  a  two  months'  human  foetus.     His,  Cajal. 
a,  Layer  of  germinal  cells;  b,  nuclear  layer;  c,  mantle  layer;  d,  marginal  layer;  e,  germinal  cell 

FIG.  490. — Section  through  the  pallial  wall  of  a  human  foetus  at  the  beginning  of 

the  third  month.     His,  Cajal. 

a,  Layer  containing  germinal  cells;  b,  fibrous  (medullary)  layer  (rudimentary  white  matter);  c,  layer 
of  neuroblasts  forming  rudimentary  cortical  gray  matter;  d,  marginal  layer  (future  molecular 
layer);  e,  germinal  cell;  /,  g,  neuroblasts  with  radial  processes.  Spongioblasts  and  myelo- 
spongium  are  shown  on  the  right  side. 

During  the  fourth  and  fifth  fcetal  months  the  cortical  layer  shows  a  differen- 
tiation into  a  denser  outer  and  an  inner  layer.  During  the  sixth  and  seventh 
months  a  differentiation  and  grouping  of  the  nerve  cells  begins  which  results 
in  the  formation  of  six  cortical  layers  (Brodmann).  These  are:  (i)  the  z'onal 


564 


TEXT-BOOK  OF  EMBRYOLOGY. 


layer  (marginal  layer,  molecular  layer  of  adult) ,  (2)  the  external  granular  layer 
(layer  of  small  pyramid  cells  of  adult),  (3)  pyramid  layer  (medium  and  large 
pyramid  cells),  (4)  internal  granular  layer,  (5)  ganglionic  layer  (internal  pyra- 
mid cells) ,  (6)  multiform  layer  (polymorphous  cells) .  By  various  local  modifi- 
cations of  this  six-layered  cortex  the  differentiation  of  the  various  histological 
areas  of  the  adult  cortex  is  brought  about.  In  the  calcarine  region  of  the 
occipital  lobe,  in  the  sixth  month,  the  internal  granular  layer  differentiates  into 


FIG.  491. — Section  through  cortex  of  a  mouse  foetus  before  birth,  showing  later  stages  of 

differentiation  of  pyramid  cells.     Golgi  method.     Cajal. 

a,  large  pyramid  cells;  b,  c.  medium-sized  and  small  pyramid  cells;  d,  beginning  collaterals  of,  e, 
axis-cylinders  or  axones;  /,  horizontal  cell  of  molecular  layer.  Basal  dendrites  of  pyramid 
cells  are  beginning  to  appear. 

two  layers  between  which  is  formed  the  line  of  Gennari  which  contains  termi- 
nations of  the  fibers  from  the  lateral  geniculate  bodies,  representing  the  visual 
pathway.  This  area  is  the  visual  cortex.  In  the  temporal  (future  transverse 
gyri)  and  postcentral  regions,  areas  are  differentiated  which  mark  the  re- 
ception of  the  terminations  of  the  fibers  of  the  acoustic  and  somaesthetic 
(medial  fillet)  pathways.  These  areas  are  thus,  respectively,  the  auditory  cortex 
and  the  somasihetic  (general  bodily  sensation)  cortex.  (Cf.  Fig.  409.) 

In  the  precentral  region,  the  internal  granular  layer  becomes  merged  with 


THE   NERVOUS   SYSTEM.  565 

the  adjoining  layers  and  practically  disappears,  the  two  inner  layers  become 
more  or  less  fused  and  in  them  certain  cells  develop  to  a  great  size  forming  the 
layer  of  giant  pyramid  cells.  It  is  the  axones  of  these  cells,  in  all  probability, 
which  proceed  as  the  pyramidal  tracts  through  the  middle  part  of  the  internal 
capsule  and  pes  to  the  epichordal  segmental  brain  and  cord.  The  area  in 
which  these  cells  lie  is  the  motor  cortex  (cf .  Fig.  409) .  Descending  axones  de- 
velop similarly  from  cells  in  the  calcarine  area,  possibly  here  also  from  large 
pyramidal  cells  of  the  fifth  and  sixth  layers  (solitary  cells  of  Meynert),  which 
probably  pass  to  the  anterior  colliculus  (operating  there  upon  reflex  eye 
mechanisms) . 

In  the  whole  pallium  there  are  thus  four  great  projection  fields,  differen- 
tiated both  by  their  histological  structure  and  their  connections.  These  are  (i) 
the  archipallial  olfactory  area  with  mesial  ascending  and  descending  connections ; 
(2)  the  visual;  (3)  the  acoustic;  (4)  the  somatic.  The  systems  of  projection  fibers 
of  the  three  neopallial  fields  are  lateral.  The  visual  and  acoustic  fields  repre- 
sent certain  specialized  and  concentrated  groups  of  receptors  (rods  and  cones, 
hair  cells  of  organ  of  Corti)  upon  which  stimuli  of  a  certain  definite  nature 
(light  and  sound  waves),  from  distant  objects,  are  focussed  by  means  of  acces- 
sory apparatus  (eye,  ear).  The  somatic  area  represents  receptors  scattered 
over  the  whole  organism.  In  the  visual  and  acoustic  mechanisms,  the  efferent 
element  is  small  or  lacking  in  both  peripheral  apparatus  and  cortical  areas,  in  the 
somatic  the  efferent  element  is  large  and  is  represented  cortically  by  an  area 
(motor,  precentral  area)  distinct  from  that  of  the  receptive  portion  (somaes- 
thetic,  postcentral  area).  Gustatory  and  other  visceral  areas  have  not  been 
well  determined  (vicinity  of  archipallium?). 

These  four  primary  sensori-motor  fields  are  probably  the  first  differentiated 
of  the  various  pallial  cortical  areas.  This  is  evidenced  by  the  myelination 
(comp.  p.  501)  which  first  involves  the  projection  fibers  of  these  areas  (at  or 
soon  after  birth,  Flechsig),  the  afferent  projection  fibers  probably  myelinating 
before  the  efferent  (Figs.  492  and  493). 

The  process  of  myelination  next  spreads  over  areas  adjoining  the  primary 
areas,  the  intermediate  areas  of  Flechsig.  Descending  projection  fibers  from 
these  areas  in  the  frontal,  temporal  and  occipital  lobes  are  probably  represented 
by  the  cortico-pontile  systems  of  fibers,  securing  cerebellar  regulation  of  pallial 
reactions.  The  presence  of  other  fibers  connecting  with  thalamic  nuclei 
is  probable,  but  knowledge  of  their  develoDment  and  connections  is  very 
incomplete. 

The  cells  whose  axones  form  descending  or  efferent  projection  fibers  con- 
stitute only  a  small  fraction  of  the  cortical  cells.  The  great  majority  are  asso- 
ciation cells  whose  axones,  or  collaterals,  pass  across  the  median  line  in  the 
lamina  terminalis  as  the  callosal  fibers  already  mentioned  (p.  557)  or  pass 


566 


TEXT-BOOK  OF  EMBRYOLOGY. 


to  distant  or  near  parts  of  the  same  hemisphere.  In  general,  these  develop  later 
than  the  projection  neurones  and  the  completion  of  their  development  is  carried 
to  a  much  later  period.  Variations  which  arise  in  their  differentiation  and  ar- 
rangement probably  contribute  largely  to  the  formation  of  various  histological 
areas  which  develop  at  different  periods.  These  local  inequalities  of  growth 
probably  constitute  a  factor  in  the  production  of  the  convolutions  appearing 
later  than  those  already  mentioned  in  connection  with  the  primary  areas.  The 
last  areas  to  myelinate,  the  terminal  areas  of  Flechsig,  are  poor  in  projection 
fibers  and  are  thus  composed  largely  (entirely  ?,  Flechsig)  of  association  cells. 
It  is  the  extent  of  these  last  developing  areas  which  constitutes  the  principal 
difference  between  the  human  cortex  and  that  of  related  forms.  These  pallial 


B 


FIG.  492. — Diagram  of  cortical  areas  of  mesial  surface  of  pallium  as  determined  by  the  myelogenetic 
method      Flechsig,  from  Quain's  Anatomy.     For  explanation  see  Fig.  493. 


areas  are  those  which  continue  to  grow  in  human  development.  Myelination 
in  the  cortical  areas  may  continue  for  twenty  years  or  so.  It  is  a  significant 
fact  that  the  last  areas  to  develop  are  comparatively  poor,  even  when  completely 
developed,  in  both  cells  and  fibers  (Campbell).  The  association  neurones 
thus  probably  follow  the  same  order  of  development  as  the  projection  systems, 
As  their  development  spreads  from  the  primary  receptive  areas  (perceptions  ?) , 
the  incoming  stimuli  receive  a  more  and  more  extended  associative  "setting" 
(psychologically,  the  "meaning"  or  "significance"  of  perceptions?),  extensive 
associations  between  the  various  areas  being  provided  by  the  extension  of  their 
development  to  the  terminal  areas  (rendering  possible  the  association  of 
symbols:  mental  processes?). 


THE  NERVOUS  SYSTEM. 


567 


The  general  biological  significance  of  this  late  development  of  the  pallium 
and  especially  of  its  associative  mechanisms  has  already  been  alluded  to. 
These  "added"  parts  of  the  nervous  system  are  the  most  modifiable  mechan- 
isms of  the  human  organism;  they  are  those  mechanisms  which  perform  its 
newest  and  most  highly  adaptive  adjustments.  The  other  parts  of  the  ner- 
vous system  are  fixed  at  birth,  but  the  cerebral  hemispheres  are  still  plastic 
for  the  reception  and  recording  of  individual  experience.  Such  experience 
symbolized  and  formulated  (spoken,  written,  etc.)  is  transmitted  to  the  next 
generation,  as  already  pointed  out  (p.  477).  An  example  of  the  far-reaching 
consequences  of  this  capacity  of  the  pallium  is  the  prolonged  period  of  infancy 
and  education  of  man. 


FIG.  493. — Diagram  of  cortical  areas  of  lateral  surface  of  pallium  as  determined  by  the  myelogenetic 

method.     Flechsig,  from  Quain's  Anatomy. 
The  numerals  indicate,  in  a  general  way;  the  order  of  myelination.     The  primary  areas  (i-io)  are 

indicated  by  dots,  the  intermediate  areas  (11-31)  by  oblique  lines  and  the  terminal  or  final 

areas  (32-36)  by  clear  spaces. 

Anomalies. 

Those  anomalies  of  the  nervous  system  involving  more  general  develop- 
mental anomalies  (cyclopia,  anencephaly,  cranioschisis,  spina  bifida,  etc.)  are 
dealt  with  in  the  chapter  on  Teratogenesis  (XIX).  Owing  to  the  fact  that  the 
nervous  system  consists  of  parts  which  are  more  or  less  separated,  and  yet  con- 
nected and  interdependent,  it  is  in  certain  respects  affected  differently  from  the 
other  organs  when  portions  of  it  are  injured  or  inhibited  in  development.  Thus 
an  injury  or  inhibition  in  development  of  one  part  of  the  nervous  system  may, 
because  of  the  dependence  upon  this  part  of  other  perhaps  distant  parts,  affect 
the  development  of  the  latter.  Even  in  the  adult,  injury  of  an  axone  leads  to  the 


508  TEXT-BOOK  OF  EMBRYOLOGY. 

disappearance  of  that  portion  of  the  axone  distal  to  the  point  of  injury;  it  may 
also  lead  to  the  disappearance  of  the  entire  neurone  where  regeneration  is  not 
possible.  Such  an  injury  during  development  will  not  only  cause  a  disappear- 
ance of  the  whole  neurone,  but  it  may  also  lead  to  the  disappearance  of  other 
neurones  forming  links  in  the  same  functional  pathway.  Thus  a  develop- 
mental defect  involving  the  central  area  will  not  only  lead  to  absence  of  the 
pyramidal  tract,  but  also  to  partial  atrophy  of  the  corresponding  fillet  bundles. 
When  one  cerebellar  hemisphere  fails  to  develop,  there  results  a  correlated 
defect  in  its  centripetal  and  centrifugal  pathways.  The  opposite  inferior  olive 
is  practically  absent,  as  is  also  the  central  tegmental  tract  leading  to  that  olive. 
The  pontile  nuclei  of  the  opposite  side,  the  middle  peduncle  leading  from  them 
to  the  affected  cerebellar  hemisphere,  and  the  fibers  in  the  pes  which  pass  to 
the  pontile  nuclei  in  question  are  likewise  suppressed,  and  the  superior 
peduncle  and  red  nucleus  are  absent  or  reduced.  In  this  case  it  is  evident  that 
the  correlated  atrophy  affects  at  least  two  neurones  in  the  pathways  leading  to 
and  from  the  cerebellum.  This  illustrates  the  far-reaching  character  of  cor- 
related developmental  defects  in  the  nervous  system  arising  from  the  nature 
of  the  connections  between  various  portions  of  the  system. 

PRACTICAL  SUGGESTIONS. 

Very  instructive  pictures  (surface  views)  of  the  neural  tube  (the  brain  vesicles,  the  spinal 
cord,  and  the  relation  of  the  latter  to  the  primitive  streak)  can  be  seen  in  chick  embryos  during 
the  second  day  of  incubation.  Remove  the  blastoderm  from  the  egg,  fix  in  Zenker's  fluid, 
stain  in  toto  with  borax-carmin,  and  mount  in  toto  in  xylol-damar.  It  is  also  interesting 
to  examine  the  blastoderm  in  the  fresh  condition.  Even  in  chick  embryos  of  later  stages, 
many  of  the  general  features  of  the  developing  nervous  system  can  be  seen  in  gross  mounts 
prepared  as  above. 

For  details  of  structure,  sections  of  embryos  must  be  made.  For  this  purpose  mam- 
malian embryos  are  usually  available.  The  sections,  if  properly  prepared,  will  serve  a  two- 
fold purpose,  viz.:  the  study  of  histological  structure  and  of  gross  form.  And  since  in  such 
complicated  organs  as  the  nervous  system  gross  form  can  be  studied  to  the  best  advantage 
by  means  of  reconstructions  (see  Appendix),  serial  sections  should  be  prepared.  Fix  the 
embryos  (pig  embryos,  for  example)  in  Bouin's  fluid,  cut  serial  transverse  sections  in  paraffin, 
stain  with  Weigert's  iron  haematoxylin  and  eosin,  and  mount  in  xylol-damar.  Orth's  fluid  and 
Zenker's  fluid  are  also  good  fixatives.  Hermann's  fluid  and  Flemming's  fluid,  followed  by 
Heidenhain's  hasmatoxylin  stain,  are  also  useful  in  the  case  of  small  embryos  (not  more 
than  8  mm.). 

While  general  histological  structure  can  be  studied  in  sections  prepared  by  the  ordinary 
technic  (as  above),  other  special  methods  are  necessary  for  the  study  of  certain  structures. 
Of  the  special  methods,  the  most  important  are  (i)  the  method  of  Golgi,  (2)  the  method  of 
Cajal,  and  (3)  the  method  of  Weigert.  All  these  have  been  more  or  less  extensively  modified. 

Method  of  Golgi. — This  has  many  modifications,  but  the  method  most  in  use  is  that  known 
as  the  Golgi  rapid  method.  This  consists  in — 

i.  Fixing  and  hardening  in  potassium  bichromate,  31/2  per  cent.,  4  vols.  +  osmic  acid, 
I  per  cent.,  i  vol.  These  proportions  may  be  varied.  The  time  of  hardening  is  very  im- 


THE   NERVOUS  SYSTEM.  569 

portant,  but  must  be  specially  determined  for  each  specimen.  In  general  it  varies  from  12 
hours  (chick  embryos  of  two  to  three  days  incubation)  to  six  or  seven  days  (e.g.,  human 
cerebral  cortex  at  birth). 

2.  The  specimen  is  next  rinsed  in  a  3/4  per  cent,  to  i  per  cent,  solution  of  silver  nitrate 
(a  previously  used  solution  will  answer  for  this  rinsing)  and  changed  until  the  solution  no 
longer  becomes  turbid  with  silver  chromate.     The  specimen  is  then  transferred  to  a  fresh 
silver  nitrate  solution  of  the  same  strength  for  24  hours,  preferably  in  the  dark.     It  is  often 
well  to  keep  the  specimen  at  this  stage  in  a  warm  chamber  at  a  temperature  of  from  25° 
to  30°  C. 

3.  The  specimen  is  next  brought  directly  into  95  per  cent,  alcohol  for  an  hour  or  more, 
the  alcohol  being  changed  several  times,  and  then  into  equal  parts  alcohol  and  ether  for 
from  1/4  to  1/2  an  hour.     It  is  next  placed  in  thin  celloidin  for  about  1/2  hour  and  then  for 
the  same  length  of  time  in  thick  celloidin.     The  specimen  is  blocked  and  the  celloidin 
hardened  quickly  in  chloroform.     Thick  sections  (50  to  70  microns)  are  cut,  cleared  in  oil 
of  origanum  Cretici,  followed  by  xylol,  and  mounted  in  xylol-balsam  or  damar,  without  a 
cover-glass.     It  is  often  of  advantage  to  transfer  the  sections  from  the  xylol  to  a  dish  of  xylol- 
balsam  or  damar  and  from  this  to  the  slide,  thereby  avoiding  diffusion  currents.     The  slides 
are  then  placed  in  the  paraffin  bath  to  hasten  the  hardening  of  the  balsam.     Sections  may  be 
mounted  under  a  cover  glass  if  melted  hard  balsam  or  damar  is  used  instead  of  a  solution  of 
the   same.     If    the   balsam   in  uncovered  specimens  becomes  wrinkled  or  cracked,  heat 
applied  until  the  balsam  just  melts  (but  does  not  bubble)  will  render  it  smooth  again. 

Material  which  is  to  be  subjected  to  the  Golgi  technic  should  be  cut  into  small  pieces,  not 
exceeding  2  to  3  mm.  in  thickness  The  method  shows  a  few  of  the  neuroblasts  and  spongio- 
blasts  as  black  objects,  they  being  filled  or  encrusted  with  a  black  silver  compound.  Internal 
structure  is  of  course  not  shown.  The  method  is  capricious  and  is  best  used  when  there  is 
considerable  material  available. 

Methods  of  Cajal. — Of  these  the  most  generally  useful  is  as  follows: 

1.  Specimens  not  more  than  5  or  6  mm.  in  thickness  are  fixed  and  hardened  for  twenty- 
four  hours  in  strong  alcohol  or  in  strong  alcohol  to  every  100  c.c.  of  which  from  four  to 
twelve  drops  of  strong  ammonia  have  been  added. 

2.  The  specimen  is  next  rinsed  in  distilled  water  or  simply  placed  in  the  water  until  it 
sinks  and  then  transferred  to  a  i  if  2  per  cent,  aqueous  solution  of  silver  nitrate.    The  strength 
of  the  silver  solution  may  be  varied  from  1/2  per  cent,  to  4  per  cent.,  11/2  per  cent,  being  the 
strength  most  commonly  employed.     While  in  the  silver  solution  the  specimens  should  be 
kept  in  the  dark  and  at  a  temperature  of  32°  to  38°  C.     The  exact  time  the  specimens  should 
remain  in  the  silver  solution  must  be  determined  by  experiment  in  each  case,  but  is  usually 
from  three  to  six  days. 

3.  The  specimen  is  next  rinsed  quickly  in  distilled  water  and  then  placed  for  twenty- 
four  hours  at  room  temperature  in 

Pyrogallol,     i  to  2  grams 
Water,  100  c.c. 

Formalin,       5  to  10  c.c. 

The  solution  should  be  freshly  made  up  and  changed  after  the  specimen  is  put  in  it  if  it 
becomes  turbid. 

4.  The  specimen  may  be  embedded  in  celloidin  or  paraffin  and  cut  in  the  usual  way 
and  about  the  usual  thickness.     Dehydrate,  clear  in  carbol-xylol  and  xylol,  and  mount  in 
xylol -damar. 


570  TEXT-BOOK  OF  EMBRYOLOGY. 

Another  in  toto  silver  method  is  that  of  Bielschowsky,  modified  by  Paton.  This  method 
is  more  complicated,  as  is  also  Bielschowsky's  important  method  of  staining  sections. 

None  of  the  silver  methods  has  an  absolutely  reliable  technic,  especially  for  embryological 
work.  They  are  particularly  designed  to  bring  out  the  neurofibrils  which  are  often  sharply 
and  deeply  stained.  The  non-neurofibrillar  portions  of  the  cell-body  and  its  processes  are 
also  often,  especially  in  the  adult,  clearly  defined  though  not  so  deeply  stained.  The 
picture  is  thus  a  more  general  one  than  that  yielded  by  the  methods  of  Golgi  and  reveals 
important  details  of  internal  cell  structure.  It  is,  however,  inferior  to  the  Golgi  methods  in 
displaying  the  finest  ramifications  of  the  processes. 

Weigerts  Method. — For  studying  myelination,  the  method  of  Weigert  or  one  of  its 
modifications  is  used.  The  specimen  is  fixed  and  hardened  in  Miiller's  fluid,  or  preferably 
fixed  for  two  or  three  days  in  Miiller's  fluid  9  vols.,  formalin  i  vol.  (the  fluid  being  changed 
once  or  twice),  and  then  hardened  for  three  or  four  weeks  in  Miiller's  fluid.  After  a  short 
washing  in  water  the  specimen  is  carried  through  graded  alcohols,  the  alcohol  being  changed 
until  the  bichromate  no  longer  colors  it.  If  the  specimen  is  kept  in  the  dark,  precipitation 
of  the  bichromate  is  avoided.  The  specimen  is  embedded  in  celloidin  or  paraffin  and 
sectioned  in  the  usual  way. 

In  the  unmodified  Weigert  method,  the  sections  are  carried  from  water  into  a  saturated 
or  half  saturated  aqueous  solution  of  neutral  cupric  acetate  for  twelve  to  twenty-four  hours. 
They  are  then  rinsed  in  water  until  the  free  cupric  acetate  is  removed,  and  transferred  to  a 
mixture  of  9  vols.  of  No.  i  solution  and  i  vol.  of  No.  2. 

No.  i.  Water,  100  c.c. 

Saturated  aqueous  solution  lithium  carbonate,  i  or  2  c.c. 
No.  2.  Haematoxylin,  10  grams. 

Alcohol,  95  per  cent,  or  absolute,  100  c.c. 

Solution  No.  2  should  be  a  week  or  more  old.     Sections  should  remain  in  the  above  mix- 
ture for  from  twelve  to  twenty-four  hours  and  are  then  differentiated  in  the  following- 
Potassium  ferricyanide,  21/2  grams. 

Borax,  2  grams. 

Water,  100  c.c. 

After  differentiation  is  complete,  the  specimens  should  be  washed  for  half  an  hour  or  more 
in  water,  dehydrated,  cleared  in  carbol-xylol  and  xylol,  and  mounted  in  xylol-damar  or 
balsam. 

The  most  important  modification  of  Weigert's  method  is  the  so-called  Weigert-Pal  method. 
This  method  should  be  used  only  with  celloidin  sections.  The  sections  are  transferred 
directly  into  either  a  10  per  cent,  solution  of  haematoxylin  in  alcohol,  i  vol.  +  water,  9  vols.,  or 
into  i  vol.  of  the  hagmatoxylin  solution  +  9  vols.  of  a  i  per  cent,  or  2  per  cent,  solution  of 
acetic  acid. 

If  the  material  has  been  kept  in  alcohol  for  some  time,  it  may  be  advisable,  before  staining* 
to  mordant  for  from  one  to  several  days  in  5  per  cent,  potassium  bichromate  or  in  Miiller's 
fluid.  Copper  bichromate,  2  per  cent,  to  3  per  cent.  (12  hours),  is  a  stronger  mordant,  but 
may  make  the  sections  brittle. 

When  stained,  the  sections  are  rinsed  in  water  and  differentiated  as  follows;  First  place 
in  a  freshly  made  1/5  per  cent,  to  1/3  per  cent,  solution  of  potassium  permanganate, 
usually  about  1/2  minute,  then  rinse  in  water  and  transfer  to 

Potassium  sulphite  i  gram. 

Oxalic  acid,  i  gram 

Water,  200  c.c. 


THE  NERVOUS   SYSTEM.  571 

This  completes  the  differentiation.  A  very  weak  solution  of  sulphurous  acid  answers  as  well 
as  or  better  than  the  sulphite-oxalic  mixture.  If  differentiation  is  not  sufficient,  rinse  in 
water  and  repeat  the  process.  After  differentiation,  dehydrate,  clear,  and  mount  as  usual. 

It  is  often  advantageous,  especially  in  younger  foetuses,  to  fix  in  copper  bichromate/3 
per  cent,  to  5  per  cent.,  9  vols.  +  formalin  i  vol.,  and  then  harden  a  week  or  more  in  copper 
bichromate,  3  per  cent.  These  specimens  should  not  be  over  i  /2  an  inch  in  thickness. 

For  all  Weigert  methods,  the  most  satisfactory  fixation  may  be  had  by  injecting  the 
bichromate-formalin  mixture  into  the  blood  vessels.  Specimens  fixed  and  preserved  in 
formalin  may  be  used  for  staining  by  the  Weigert  method.  Mordant  pieces  in  copper 
bichromate  3  per  cent,  about  a  week  or  use  the  methods  given  in  Mallory  and  Wright's 
"  Pathological  Technic. " 

For  further  details  and  other  modifications  of  Weigert's  methods,  the  student  is  referred 
to  the  books  on  technic  mentioned  in  the  Appendix. 

References  for  Further  Study. 

BARDEEN,  C.  R.:  The  Growth  and  Histogenesis  of  the  Cerebrospinal  Nerves  in  Mam- 
mals. Am.  Jour,  of  Anat.,  Vol.  II,  No.  2,  1903. 

DEJERINE,  J.:    Anatomic  des  centres  nerveux.     Tome  I,  Ch.  2  and  3. 

EDINGER,  L.:    Vorlesungen  iiber  den  Bau  der  nervosen  Zentralorgane.     Seventh  Ed. 

EDINGER,  L.  The  Relations  of  Comparative  Anatomy  to  Comparative  Psychology. 
Jour.  ofComp.  Neural,  and  Psychol.,  Vol.  XVIII,  No.  5,  Nov.,  1908. 

FLECHSIG,  P. :  Einige  Bemerkungen  iiber  die  Untersuchungsmethoden  der  Grosshirnrinde 
insbesondere  desMenschen.  Berichten  der  math.-phys.  Klasse  d.  Konigl -Sachs.  Gesellsch.  d. 
Wissensch.  zu  Leipzig.  1904.  See  also  Johns  Hopkins  Hasp.  Bull.,  Vol.  XVI,  1905,  pp. 

45-49- 

HARDESTY,  I.:    On  the  Development  and  Nature  of  the  Neuroglia.     Am.  Jour,  of  Anat., 

Vol.  Ill,  No.  3,  July,  1904. 

HARRISON,  R.  G. :  Further  Experiments  on  the  Development  of  Peripheral  Nerves. 
Am.  Jour,  of  Anat.,  Vol.  V,  No.  2,  May,  1906. 

HARRISON,  R.  G.:  Observations  on  the  Living  Developing  Nerve  Fiber.  Anat.  Record, 
Vol.  I,  No.  5,  1907. 

HARRISON,  R.  G. :  Embryonic  Transplantation  and  Development  of  the  Nervous 
System.  Anat.  Record,  Vol.  II,  No.  9,  1908. 

HERRICK,  C.  J.:  The  Morphological  Subdivision  of  the  Brain.  Jour,  of  Comp.  Neural, 
and  Psychol.,  Vol.  XVIII,  No.  4,  1908. 

His,  W.:  Zur  Geschichte  des  menschlichen  Riickenmarkes  und  der  Nervenwurzeln. 
Abhandl.  der  math.-phys.  Klasse  der  Konig.-Sdchs.  Gesellsch.  d.  Wissensch.,  Bd.  XIII,  1887. 

His,  W.:  Zur  Geschichte  des  Gehirns,  sowie  der  centralen  und  peripherischen  Nerven- 
bahnen  beim  menschlichen  Embryo.  Abhandl.  d.  math.-phys.  Klasse  d.  Konig.-Sdchs. 
Gesellsch.  d.  Wissensch.,  Bd.  XIV,  1888. 

His,  W.:  Die  Neuroblasten  und  deren  Entstehung  im  embryonalen  Mark.  Abhandl.  d. 
math.-phys.  Klasse  d.  Konig.-Sdchs.  d.  Wissensch.,  Bd.  XV,  1890.  Also  Arch.  f.  Anat.  u. 
Physiol.,  Anat.  Abth.,  1889. 

His,  W.:  Ueber  die  Entwickelung  des  Riechlappens  und  des  Riechganglions  und  iiber 
diejenige  des  verlangerten  Markes.  Verhandl.  d.  Anat.  Gesellsch.  zu  Berlin,  1889.  Also 
Abhandl.  d.  math.-phys.  Klasse  d.  Konig.-Sdchs.  Gesellsch.  d.  'Wissensch.,  Bd.  XV,  1889. 

His,  W.:  Die  Entwickelung  des  menschlichen  Rautenhirns  vom  Ende  des ersten  bis  zum 


572  TEXT-BOOK  OF  EMBRYOLOGY. 

Beginn  des  dritten  Monats.  I.  verlangertes  Mark.  Abhandl.  d.  math.-phys.  Klasse  d.  Konig.- 
Sachs.  Gesellsch.  d.  Wissensch.,  Bd.  XVII,  1891. 

His,  W.:  Die  Entwickelung  des  menschlichen  Gehirns  wahrend  der  ersten  Monate. 
Leipzig,  1904. 

JOHNSTON,  J.  B.:  The  Nervous  System  of  Vertebrates.     1906. 

KOLLMANN,  J.:  Handatlas  der  Entwickelungsgeschichte  des  Menschen.     Bd.  II,  1907. 

VON  KUPFFER,  K. :  Die  Morphogenie  des  Centralnervensystems.  In  Hertwig's  Handbuch 
d.  vergleich.  u.  experiment.  Entwickelungslehre  der  Wirbellicre.  Bd.  II,  Teil  III,  Kap.  8, 
1905. 

MARBURG,  O.:  Mikroskopisch-topographischer  Atlas  des  menschlichen  Zentralnerven- 
systems,  1904, 

MEYER,  A.:  Critical  Review  of  the  Data  and  General  Methods  and  Deductions  of 
Modern  Neurology.  Jour.  ofComp.  Neural.,  Vol.  VIII,  Nos.  3  and  4,  1898. 

NEUMAYER,  L.:  Histo-  und  Morphogenese  des  peripheren  Nervensystems,  der  Spinal- 
ganglien  und  des  Nervus  sympathicus.  In  Hertwig's  Handbuch  der  vergleich.  und  experi- 
ment. Entwickelungslehre  der  Wirbeltiere,  Bd.  II,  Teil  III,  Kap.  10,  1906. 

RAMON  Y  CAJAL,  S. :  Sur  1'origine  et  les  ramifications  des  fibres  nerveuses  de  la  moelle 
embryonnaire.  Anat.  Anz.,  Bd.  V,  Nos.  3  and  4,  1890. 

RAMON  Y  CAJAL,  S.:  A  quelle  epoque  apparaissent  les  expansions  des  cellules  nerveuses 
de  la  moelle  epiniere  du  poulet?  Anat.  Anz.,  Bd.  V,  Nos.  21  and  22,  1890. 

RAMON  Y  CAJAL,  S.:  Textura  del  sistema  nervioso  del  hombre  y  de  los  vertebrados. 
Madrid,  1899-1904.  Also  translation  into  French  by  Azoulay,  1910-11. 

RAMON  Y  CAJAL,  S.:  Nouvelles  observations  sur  1'evolution  des  neuroblasts,  avec  quel- 
ques  rernarques  sur  Phypothese  neurogenetique  de  Hensen-Held.  Anat.  Anz.,  Bd.  XXXII, 
Nos.  i,  2,  3  and  4,  1908. 

SCHAPER,  A.:  Die  morphologische  und  histologische  Entwickelung  des  Kleinhirns  der 
Teleostier.  Morph.  Jahrbuch,  Bd.  XXI,  1894. 

SCHAPER,  A.:  Die  friihesten  Differenzierungsvorgange  im  Centralnervensystems.  Arch, 
f.  Entw.-Mechan.,  Bd.  V,  1897. 

SMITH,  G.  E.:  On  the  Morphology  of  the  Cerebral  Commissures  in  the  Vertebrata,  etc. 
Trans.  Linn&an  Soc.  of  London,  2d  Ser.  Zoology,  Vol.  VIII,  Part  12,  1903.  See  also  articles 
by  same  author  in  Jour,  of  Anat.  and  Physiol. 

STREETER,  G.  L.:  The  Development  of  the  Cranial  and  Spinal  Nerves  in  the  Occipital 
Region  of  the  Human  Embryo.  Am.  Jour,  of  Anat.,  Vol.  IV,  No.  i,  1904. 

STREETER,  G.  L.:  The  Peripheral  Nervous  System  in  the  Human  Embryo  at  the  End 
of  the  First  Month.  Am.  Jour,  of  Anat.,  Vol.  VIII,  No.  3. 

ZIEHEN,  TH.  :  Die  Morphogenie  des  Centralnervensystems  der  Saugetiere.  In  Hertwig's 
Handbuch  der  vergleich.  u.  experiment.  Entwickelungslehre  der  Wirbeltiere.  Bd.  II,  Teil  III, 
Kap.  8,  1905. 

ZIEHEN,  TH.:  Die  Histogenese  von  Him-  und  Ruckenmark.  Entwickelung  der 
Leitungsbahnen  und  der  Nervenkerne  bei  den  Wirbeltiercn.  In  Hertwig's  Handbuch  der 
vergleich.  u.  experiment  Entwickelungslehre  der  Wirbelliere,  Bd.  II,  Teil  III,  Kap.  IX,  1905. 


CHAPTER  XVIII. 

THE  ORGANS  OF  SPECIAL  SENSE. 
THE  EYE. 

The  receptive  mechanisms  of  all  the  general  and  special  sense  organs 
are  derived  from  the  ectoderm.  With  the  single  exception  of  the  eye,  all 
develop  as  direct  specializations  of  the  ectoderm  in  the  form  of  the  various 
neuro-epithelia.  The  eye  is  peculiar  among  the  sense  organs  in  that  its  recep- 
tive cells  are  not  derived  directly  from  surface  ectoderm,  but  only  indirectly  from 
the  ectoderm  after  it  has  become  folded  in  to  form  the  neural  canal.  The 
neuro-epithelium  of  the  eye  develops  as  a  direct  outgrowth  from  the  central 
nervous  system.  The  retina  is  a  modified  part  of  the  brain;  the  optic  nerves 
correspond  to  central  nervous  system  fiber  tracts.  Of  the  accessory  optic 
structures,  the  lens,  the  epithelium  of  the  lids  and  conjunctiva,  the  eyelashes, 
the  Meibomian  glands  and  the  epithelium  of  the  lacrymal  apparatus  are  of 
ectodermic  origin;  the  coats  of  the  eye.  the  sclera  and  chorioid,  and  parts  of 

Optic  Neural  Optic 

depression  plate  depression 


FIG.  494.— Diagram  showing  location  of  optic  areas  before  the  closure  of  the  neural  groove. 

Modified  from  Lange. 

their  modified  anterior  extensions,  the  cornea,  ciliary  body  and  iris,  are  of 
mesodermic  origin.  In  the  sensory  divisions  of  the  other  spinal  and  cranial 
nerves,  with  the  exception  of  the  olfactory,  the  cell  bodies  of  the  neurones  which 
serve  to  connect  the  receptive  mechanisms  with  the  brain  and  cord  are  located 
in  parts  (the  sensory  ganglia  of  the  cranial  and  spinal  nerves)  which  have  be- 
come separated  from  the  crests  of  the  neural  folds  as  the  latter  fuse  to  form  the 
neural  canal.  In  the  eye  the  cell  bodies  of  these  neurones  are  located  in  the 
retina,  but  the  area  of  ectoderm  from  which  the  retina  develops  first  occupies  a 
position  along  the  neural  crest  analogous  to  that  occupied  by  the  anlagen  of  the 
spinal  and  cranial  ganglia.  In  the  case  of  the  retina  this  area,  instead  of  be- 
coming split  off  in  the  closure  of  the  neural  canal,  becomes  folded  into  the 
canal  and  later  pushed  out  toward  the  surface  in  the  optic  evagination  (Figs.  494, 
495,  49°)  • 

573 


574 


TEXT-BOOK  OF  EMBRYOLOGY. 


The  first  indication  of  eye  formation  is  found  in  the  chick  at  the  beginning 
of  the  second  day  of  incubation ;  in  the  human  embryo,  at  what  has  been  estimated 
as  about  the  second  or  third  week.  At  this  stage  the  neural  canal  is  not  yet 
completely  closed  in  and  its  anterior  end  shows  three  primary  brain  vesicles 


Optic  vesicle  area 


Neural  canal 

FIG.  495. — Diagram  showing  location  of  areas  shown  in  Fig.  494  after  the  formation  of  the 
neural  canal.     Modified  from  Lange. 

(p.  480,  Fig.  497).  The  anlagen  of  the  eyes  first  appear  as  bilaterally  sym- 
metrical evaginations  from  the  lateral  walls  of  the  fore-brain  vesicle  (Figs.  497  and 
498),  and  are  at  first  large  in  proportion  to  the  brain  vesicle  itself.  When 
first  formed,  the  optic  evagination  opens  widely  into  the  fore-brain  vesicle  (Fig. 
498,  right  side),  but  as  the  distal  part  of  the  evagination  expands  more  rapidly 


Retina 


H-b. 


Optic  stalk 


FIG.  496.  FIG.  497. 

FIG.  496. — Diagram  showing  location  of  the  (dark)  optic  area  (see  Fig.  495)  after  the  beginning  of 
the  formation  of  the  optic  cup  and  optic  stalk.     Lange. 

FiG.  497. — Dorsal  view  of  head  of  chick  of  58  hours'  incubation.     Mihalkovics. 

Lam.  term,  lamina  terminalis;  Fb.,  fore-brain;  Opt.  v.,  optic  vesicle;  M. b.,  mid-brain; 

H.b.,  hind  or  rhombic  brain;  H.,  heart. 

than  the  proximal  part,  there  soon  results  a  spheroidal  optic  vesicle  attached  to 
the  fore-brain  by  the  narrow  optic  stalk  (Fig.  498,  left  side).  Through  the  latter 
the  cavity  of  the  optic  vesicle  and  the  cavity  of  the  fore-brain  are  in  communi- 
cation. With  the  development  of  the  hemispheres,  that  part  of  the  brain  to 
which  the  optic  stalks  are  attached  becomes  the  inter-brain  (diencephalon). 


THE   ORGANS   OF  SPECIAL  SENSE. 


575 


The  Lens. — As  each  optic  vesicle  grows  out  toward  the  surface,  its  outer 
wall  soon  comes  to  lie  just  beneath  the  surface  ectoderm.  The  cells  of  that 
portion  of  the  ectoderm  which  overlies  the  optic  vesicle  next  proliferate  and 
cause  a  thickening  of  the  ectoderm  (Fig.  498,  left  side).  This  thickening  of  the 


Fore-brain  vesicle 


Lens  area  -  iv 


Optic  vesicle 


Surface  ectoderm 


Optic  vesicle 


FIG.  498. — Section  through  head  of  chick  of  two  days'  incubation.     Duval. 

The  formation  of  the  optic  vesicle  and  stalk  appears  to  be  somewhat  more  advanced 

on  the  left  than  on  the  right. 

ectoderm  over  the  optic  vesicle  is  apparent  in  the  chick  embryo  of  36  hours  in- 
cubation; in  the  human  embryo  it  occurs  about  the  third  or  fourth  week  and 
represents  the  first  step  in  the  development  of  the  crystalline  lens.  The  thick- 
ened portion  of  ectoderm  is  known  as  the  lens  area  (Fig.  498).  The  latter  next 

Fore-brain 


Lens  invagination  -  -  - -p,^      JSJ: .' S3  ^- '. ffl   M \ ^C':'  Lens  invagination 

Optic  vesicle 

Optic  vesicle 

FIG.  499. — Section  through  head  of  chick  of  three  days'  incubation.     Duval. 

becomes  depressed  against  the  outer  surface  of  the  optic  vesicle  forming  a 
distinct  lens  invagination  (Fig.  499).  This  becomes  cup-shaped  and  then  its 
edges  come  together  and  fuse,  thus  forming  the  lens  vesicle  (Fig.  500) .  At  first  the 
lens  vesicle  is  connected  with  the  surface  ectoderm,  but  about  the  eighth  week 

37 


576 


TEXT-BOOK  OF  EMBRYOLOGY. 


a  thin  layer  of  mesoderm  grows  in  between  the  lens  vesicle  and  the  surface 
ectoderm,  completely  separating  them  (Fig.  501).  The  ingrowth  of  the  lens 
vesicle  against  the  outgrowing  optic  vesicle  has  the  effect  as  though  a  small  hard 
ball  (the  lens  vesicle)  had  been  pressed  into  a  larger  soft  ball  (the  optic  vesicle) 


Fore-brain , 


Lens  vesicle  - 


Optic  cup  •  ' 


FIG.  500. — Showing  somewhat  later  stage  in  development  of  optic  cup  and  lens 
than  is  shown  in  Fig.  499.     DuvaJ,. 

' 

(Fig.  502).  The  lens  vesicle  pushes  the  outer  wall  of  the  optic  vesicle  in  against 
the  inner  wall,  the  optic  vesicle  thus  becoming  transformed  into  the  two-layered 
optic  cup  (Figs.  500,  501).  Bonnet  calls  attention  to  the  fact  that  the  two  proc- 
esses, lens  formation  and  the  invagination  of  the  optic  vesicle  to  form  the  optic 


Conjunctival  epithelium -* 


Vitreous  —  * 


Lens  vesicle 


Retina  (inner  layer 
of  optic  cup)  ' 


Optic  stalk 


Pigmented  layer  of  retina 

(outer  layer  of  optic  cup) 

FIG.  501. — Diagram  of  developing  lens  and  optic  cup.     Duval. 

The  cells  of  the  inner  wall  of  the  lens  vesicle  have  begun  lo  elongate  to  form  lens  fibers.  The  epi- 
thelium over  the  lens  is  the  anlage  of  the  corneal  epithelium.  The  mesodermal  tissue  between 
the  latter  and  the  anterior  wall  of  the  lens  vesicle  is  the  anlage  of  the  substantia  propria 


cup,  are  more  or  less  independent  and  that  it  is  not  correct  to  describe  the  lens  as 
actually  pushing  in  the  outer  wall  of  the  vesicle.  As  evidence  of  this  is  noted 
the  fact  that  typical  optic  cup  formation  may  occur  in  cases  where  no  lens  is 
developed.  The  optic  cup  when  first  formed  is  not  a  complete  cup,  for  the 


THE   ORGANS   OF  SPECIAL  SENSE. 


577 


invagination  of  the  optic  vesicle  is  carried  over  along  the  posterior  surface  of  the 
optic  stalk  forming  the  chorioidal  fissure  (Fig.  502,  see  also  p.  585). 

The  lens  area  is  thicker  at  its  center  than  at  its  periphery  and  when  the 
center  of  the  lens  area  becomes  the  bottom  of  the  lens  depression  and  later 
the  posterior  wall  of  the  lens  vesicle  this  greater  thickness  is  maintained.  In 
fact,  the  posterior  wall  of  the  vesicle  becomes  still  thicker  so  that  it  projects  into 
the  cavity  of  the  lens  vesicle  as  an  eminence  (Fig.  503,  g.) .  In  the  chick  the  lens 
vesicle  is  hollow.  In  man  and  in  Mammals  generally  it  is  more  or  less  filled 
with  cells.  These,  however,  degenerate  and  take  no  part  in  the  formation  of  the 


Pigmented  layer  of  retina 
(outer  layer  of  optic  cup) 


Nervous  layer  of  retina 
(inner  layer  of  optic  cap) 


Cavity  of 
optic  vesicle 


Optic  furrow 


Rim  of  optic  cup. 


Lens 


Hyaloid  artery  I      Optic  furrow 

Hyaloid  artery  entering 
cavity  of  vitreous 

FIG.  502. — Model  showing  lens  and  formation  of  optic  cup.  A  piece  has  been  removed  from  the 
upper  part  of  cup  to  show  the  cavity  of  the  optic  vesicle  and  the  position  of  the  inner  layer 
of  the  cup  (nervous  layer  of  retina).  Bonnet. 

permanent  lens.  Comparing  the  posterior  with  the  anterior  wall  of  the  lens  at  this 
stage,  the  latter  is  seen  to  be  composed  of  a  single  layer  of  cuboidal  cells,  the  an- 
lage  of  the  anterior  epithelium  of  the  lens  (Figs.  501 ,  503,  g,  h,  i) .  This  layer  passes 
over  rather  abruptly  into  the  posterior  wall  which  consists  of  a  single  layer  of 
greatly  elongated  lens  cells,  the  anlagen  of  the  lens  fibers.  The  lens  fibers  con- 
tinue to  elongate  until  by  the  end  of  the  second  month  they  touch  the  anterior 
epithelium,  thus  completely  obliterating  the  cavity  of  the  lens  vesicle  (Fig.  505). 
A  small  cleft  containing  a  few  drops  of  fluid,  the  liquor  Morgagni,  may  remain 
between  the  anterior  epithelium  and  the  lens  fibers. 

When  the  lens  fibers  are  first  formed,  the  longest  fibers  are  in  the  center  and 
the  fibers  gradually  get  shorter  toward  the  periphery  of  the  lens  where  they  pass 
over  into  the  anterior  epithelium  (Fig.  503),  As  the  lens  develops,  the  periph- 


578 


TEXT-BOOK  OF  EMBRYOLOGY. 


eral  fibers  elongate  more  rapidly  than  the  central,  with  the  result  that  in  the  fully 
developed  lens  the  central  fibers  are  the  shortest,  forming  a  sort  of  core  around 
which  the  now  longer  peripheral  fibers  extend  in  much  the  same  manner  as  the 
layers  of  an  onion  (Fig.  505).  The  ends  of  the  fibers  meet  on  the  anterior  and 
posterior  surfaces  of  the  lens,  along  more  or  less  definite  lines  which  can  be  seen 


FIG.  503. — Successive  stages  in  the  development  of  the  lens  in  the  rabbit  embryo.     Rabl. 

a,  b,  c,  d,  and  e,  are  from  embryos  of  from  n^  to  12  days;  f,  at  end  of  i2th  day;  g,  during  the  I3th 

day;    h,  between  the  i3th  and  i4th  days;  i,  from  an  embryo  of  n  mm. 

on  surface  examination  and  which  are  known  as  sutural  lines.  The  lens  fibers 
are  at  first  all  nucleated  and  as  the  nuclei  are  situated  at  approximately  the  same 
level  in  all  the  fibers,  there  results  a  so-called  nuclear  zone  (Fig.  503,  i).  Later 
the  nuclei  disappear.  The  sutural  lines  become  evident  about  the  fifth  month 
and  mark  the  completion  of  the  lens  formation,  although  lens  fibers  continue 
to  be  formed  throughout  foetal  and  in  postnatal  life,  probably  by  proliferation 


THE   ORGANS   OF  SPECIAL  SENSE  579 

and  differentiation  of  the  cells  of  the  anterior  epithelium,  in  the  region  where  the 
latter  pass  over  into  the  lens  fibers.  (The  successive  stages  in  the  development 
of  the  lens  are  shown  in  Fig.  503.) 

The  lens  capsule  becomes  differentiated  during  the  third  month.  It  is  con- 
sidered by  some  as  derived  from  the  lens  epithelium  and  of  the  nature  of  a 
cuticular  membrane,  by  others  as  a  product  of  the  surrounding  connective 
tissue. 

By  the  extension  of  mesodermic  tissue  in  between  the  lens  and  the  surface 
ectoderm,  the  lens  becomes  by  the  end  of  the  sixth  week  completely  surrounded 
by  a  layer  of  vascular  connective  tissue.  This  is  known  as  the  tunica  vasculosa 
lenlis,  and  receives  its  blood  supply  mainly  from  the  hyaloid  artery  (Fig.  505) 
which  is  a  fcetal  continuation  of  the  arteria  centralis  retina  (p.  585).  Branches 
from  the- hyaloid  artery  break  up  into  a  capillary  network  which  covers  both 
anterior  and  posterior  surfaces  of  the  lens.  That  part  of  the  tunica  vasculosa 
which  covers  the  anterior  surface  of  the  lens  is  known  as  the  membrana  pupittaris. 
After  the  earlier  and  more  rapid  formation  of  lens  fibers  ceases,  the  hyaloid 
artery  begins  (about  the  seventh  month)  to  undergo  regressive  changes,  and  at 
birth  is  normally  absent.  Rarely  more  or  less  of  the  tunica  vasculosa  fails  to 
degenerate,  and  if  the  part  which  persists  is  the  membrana  pupillaris  there 
results  a  malformation  known  as  congenital  atresia  of  the  pupil. 

The  Optic  Cup. —  The  way  in  which  the  optic  vesicle  becomes  transformed 
into  the  optic  cup  has  been  partially  described  in  considering  the  development  of 
the  lens  (p.  576).  The  growing  lens  vesicle  appears  to  push  in  the  outer  wall  of 
the  optic  vesicle  while  at  the  same  time  the  edges  of  the  latter  are  extending 
around  the  lens  vesicle,  until  what  was  originally  the  outer  wall  of  the  optic 
vesicle  lies  in  apposition  with  the  original  inner  wall,  the  cavity  of  the  primary 
optic  vesicle  thus  becoming  completely  obliterated  (Fig.  504).  In  this  way  the 
optic  vesicle  is  transformed  into  a  two-layered  thick-walled  cup,  the  cleft  be- 
tween the  two  layers  corresponding  to  the  cavity  of  the  primary  vesicle.  This 
cup  is  at  first  entirely  filled  with  the  developing  lens  (Fig.  504).  As  the  cup  in- 
creases in  size  faster  than  the  lens,  the  contiguous  walls  of  the  cup  and  lens 
become  separated,  the  cavity  thus  formed  being  the  cavity  of  the  vitreous 
humor  (Fig.  505).  There  seems  to  be  no  question  but  that  in  Mammals  a 
small  amount  of  mesoderm  at  first  separates  the  optic  evagination  from  the  lens 
area  of  the  surface  ectoderm.  This  apparently  disappears,  however,  so  that 
the  two  are  in  direct  contact.  It  is  still  an  open  question  whether  a  thin  layer 
of  mesoderm  grows  in  between  the  edges  of  the  cup  and  the  lens  at  or  just  before 
the  beginning  of  the  formation  of  the  vitreous.  The  lens  now  no  longer  fills  the 
optic  cup  but  lies  in  the  mouth  of  the  cup,  while  at  the  same  time  the  margin 
of  the  cup  is  extending  somewhat  over  its  outer  surface,  where  with  the  meso- 
derm it  ultimately  gives  rise  to  the  ciliary  body  and  iris,  and  forms  the 


580 


TEXT-BOOK  OF  EMBRYOLOGY. 


boundary  of  the  pupil.     The  remainder  of  the  two-walled  optic  cup  becomes 
the  retina. 

The  Retina. — Of  the  two  layers  which  form  the  wall  of  the  optic  cup  (p.  579), 
the  outer  (a  way  from  the  cavity)  forms  the  pigmented  layer,  while  the  inner  forms 
the  remainder  of  the  retina  (Figs.  501,  505).  Soon  after  the  formation  of  the 
optic  cup,  it  is  possible  to  distinguish  a  boundary  zone — the  future  or  a  serrata — 
between  the  larger  posterior  part  of  the  retina  or  nervous  retina  and  the  smaller 
anterior  non-nervous  part  which  becomes  the  retinal  portion  of  the  ciliary  body 


Vascular  mesoderm 


.Remains  of  optic 
vesicle  cavity 


Ectoderm 


Lens  anlage 
Lens  invagination 


Pigmented  layer  of  retina 
(outer  layer  of  optic  cup) 


Vascular  mesoderm 
Wall  of  brain  vesicle 


FIG.  504. — Section  through  optic  cup  and  lens  invagination  of  chick  of  fifty-four 

hours'  incubation.     Lange. 

Between  the  lens  anlage  and  the  pigmented  layer  of  the  retina  is  the  broad  inner  layer  of  the  optic 
cup,  the  anlage  of  the  remainder  of  the  retina. 


and  iris.  While  the  optic  cup  is  forming,  its  two  layers  are  both  rapidly  in- 
creasing in  thickness  by  mitotic  division  of  their  cells.  Especially  is  this  true  of 
the  inner  layer  over  that  region  which  is  to  become  the  nervous  retina,  and  it  is 
the  rather  abrupt  transition  between  the  thicker  nervous  retina  and  the  com- 
paratively thin  non-nervous  anterior  extension  of  the  retina  that  forms  the  ora 
serrata. 

The  invagination  which  gives  rise  to  the  two-layered  optic  cup  thus  differen- 
tiates what  may  be  called  the  two  primary  layers  of  the  retina,  the  pigmented  layer, 
and  a  broad  layer  from  which  are  to  develop  all  the  other  layers  of  the  retina. 


THE   ORGANS   OF  SPECIAL  SENSE. 


581 


(Figs.  501 , 505) .  Further  development  consists  in  a  gradual  differentiation,  within 
the  broad  layer,  of  the  various  retinal  elements  and  consequent  demarcation  of  the 
layers  which  constitute  the  adult  retina.  The  next  layer  to  differentiate  is  the 
innermost  layer  of  the  retina,  or  layer  of  nerve  fibers.  This  appears  during  the 
sixth  or  seventh  week  as  a  thin,  clear,  faintly  striated  zone  containing  a  few 
scattered  nuclei.  What  remains  of  the  original  inner  layer  of  the  cup  has  now 
become  a  comparatively  thick  layer  with  numerous  chromatic  and  actively 
dividing  nuclei.  It  may  be  conveniently  designated  the  primitive  nuclear  layer. 


Surface  epithelium 

of  eyelid 

Eyelid  (upper) 

Corneal  epithelium 

Conjunct:  val 

epithelium 

Substantia 

propria  cornea 

Lens 

Anterior  epithe- 
lium of  lens 

Conjunctival  sac 


Chorioid 
Pigmented  layer 
of  retina 
Split  between 
retinal  layers 
Retina,  except 
pigmented  layer 
Vitreous 

Tunica  vasculosa 
lentis 

Nerve  fiber  layer 
of  retina 


Hyaloid  artery 

Central  artery 
of  retina 

Optic  nerve 


FIG.  505. — Horizontal  section  through  eye  of  human  embryo  of  13-14  weeks.     Modified  from  Lange. 

The  similarity  in  development  between  the  retina  and  wall  of  the  neural  tube 
is  to  be  noted.  Thus  the  layer  of  nerve  fibers  appears  to  correspond  quite 
closely  to  the  marginal  layer  of  the  central  nervous  system,  while  the  primitive 
nuclear  layer  is  probably  homologous  with  the  mantle  layer  (pp.  486,  492). 
There  is  a  similar  correspondence  between  the  retina  and  the  central  nervous 
system  in  regard  to  their  early  cellular  development,  the  retinal  cells  early 
showing  a  differentiation  into  neuroblasts  and  spongiobiasts  (pp.  486,  492). 

About  the  end  of  the  eighth  week  the  inner  part  of  the  primitive  nuclear 
layer  differentiates  into  the  layer  of  ganglion  cells  (Fig.  506,  li).  These 
are  large  cells  and  with  their  processes  constitute  the  third  or  proximal  optic 
neurone.  They  can  be  first  distinguished  in  the  fundus  of  the  cup  and  gradu- 
ally extend  to  the  ora  serrata.  They  are  the  first  of  the  cellular  elements  of  the 
adult  retina  which  can  be  definitely  recognized  as  such.  From  each  cell,  two 
kinds  of  processes  develop,  dendrites,  which  ramify  in  this  and  in  the  more 
external  layers  of  the  retina,  and  an  axone  which  grows  toward  the  cavity  of 
the  eye  and  becomes  a  fiber  of  the  layer  of  nerve  fibers,  whence  it  continues  into 


582 


TEXT-BOOK  OF  EMBRYOLOGY. 


the  optic  stalk  as  one  of  the  fibers  of  the  optic  nerve.  The  layer  of  ganglion  cells 
is  thickest  in  an  area  situated  somewhat  lateral  to  the  attachment  of  the  optic 
stalk  and  known  as  the  area  centralis.  It  is  distinguishable  about  the  end  of  the 
fourth  month.  In  the  center  of  the  area  centralis  the  retinal  layers  become 
thin  to  form  the  fovea  centralis  which  develops  toward  the  end  of  foetal  life. 
The  macula  lutea  with  its  yellow  pigment  does  not  develop  until  after  birth. 
The  retina  at  this  stage  thus  consists  of  four  layers  which  from  within  out- 
ward are  (i)  the  layer  of  nerve  fibers,  (2)  the  layer  of  ganglion  cells,  (3)  the 
nuclear  layer,  (4)  the  pigmented  layer  (see  Fig.  507). 


FIG.  506. — Diagram  of  the  development  of  the  retinal  cells.     Kallius,  after  Cajal. 
a,  Cone  cells  in  unipolar  stage;  b,  cone  cells  in  bipolar  stage;  c,  rod  cells  in  unipolar  stage;  d,  rod  cells 
in  bipolar  stage;  e,  bipolar  cells;  /and  i,  amacrine  cells;  g,  horizontal  cell;  h,  ganglion  cells; 
k,  Muller's  cells  or  fibers;  /,  external  limiting  membrane. 

The  further  development  of  the  retina  consists  largely  of  a  differentiation  of 
the  cells  of  the  nuclear  layer.  This  is  extremely  complex  and  our  knowledge 
of  it  meager.  From  the  cells  of  this  layer  develop  (i)  the  rod  and  cone  cells,  (2) 
the  bipolar  cells,  (3)  the  tangential  or  horizontal  cells,  (4)  the  amacrine  cells,  (5) 
Muller's  cells  or  fibers.  The  differentiation  of  these  cells  and  their  processes 
also  results  in  the  demarcation  of  the  following  layers  of  the  adult  retina;  (i)  the 
layer  of  rods  and  cones,  (2)  the  outer  limiting  membrane,  (3)  the  outer  nuclear 
layer,  (4)  the  outer  molecular  layer,  (?)  the  inner  nuclear  layer,  (6)  the  inner 
molecular  layer,  (7)  the  inner  limiting  membrane  (see  Fig.  508). 

Muller's  cells  or  the  sustentacular  cells  (Fig.  506,  k)  develop  from  spongio- 
blasts  which  lie  toward  the  inner  limit  of  the  nuclear  layer.  This  accounts 
for  the  location  of  the  nucleated  portions  of  Muller's  cells.  Processes  of  these 
cells  grow  toward  both  surfaces  of  the  retina  until  they  reach  the  positions  of  the 
future  outer  and  inner  limiting  membranes  where  they  are  believed  to  spread  out 


THE   ORGANS   OF  SPECIAL  SENSE. 


583 


horizontally  and  unite  to  form  these  membranes.  Other  spongioblasts  develop 
into  other  types  of  glia  cells,  mainly  spider  cells,  which  are  most  numerous  in 
the  layer  of  ganglion  cells  and  in  the  layer  of  nerve  fibers. 

The  rod  and  cone  cells  are  first  recognizable  as  unipolar  cells  (Fig.  506, a,  c). 
The  single  process  of  each  extends  outward  as  far  as  the  outer  limiting  mem- 
brane. About  as  soon  as  these  cells  are  recognizable,  a  differentiation  between 
the  rod  cells  and  the  cone  cells  can  be  made  by  their  reactions  to  the  Golgi 
silver  stain,  the  cone  cells  impregnating  much  more  completely  than  the  rod 
cells.  Processes  next  grow  out  from  the  inner  ends  of  the  cells  so  that  they 
become  bipolar  (Fig.  506,  b,  d) .  Both  rod  and  cone  cells  are  at  first  distributed 
throughout  the  entire  nuclear  layer,  but  later  they  become  arranged  in  a  dis- 
tinct layer  just  beneath  the  outer  limiting  membrane.  Each  cell  next  gives 
rise  to  or  acquires  at  its  outer  end  an  expansion  which  extends  through 


Outer  undifferentiated  layer 


FIG.  507.-*- Vertical  section  through  retina  of  a  four  months'  human  embryo.    Modified  from  Lange. 


the  outer  limiting  membrane  into  the  pigmented  layer.  As  the  pigmented 
cells  give  off  pigmented  processes  which  extend  inward  among  the  outer 
ends  of  the  rods  and  cones,  the  layer  of  retina  just  beneath  the  pig- 
mented layer  consists  of  the  outer  ends  of  the  rod  cells,  the  tips  of  the  cone 
cells,  and  the  extensions  of  the  pigmented  cells.  The  nucleated  portions  of 
the  rod  and  cone  cells  form  the  outer  nuclear  layer.  Though  the  layer  of  rods 
and  cones  and  the  outer  nuclear  layer  present  the  appearance  in  haematoxylin- 
eosin  stained  specimens  of  two  distinct  layers,  it  is  evident  from  their  develop- 
ment and  structure  that  they  should  be  regarded  as  a  single  neuro-epithelial 
layer.  The  apparent  separation  into  two  layers  is  due  to  the  interposition  of  the 
outer  limiting  membrane,  through  tiny  holes  in  which  the  rod  and  cone  cells 
extend.  The  inwardly  directed  processes  of  the  rod  and  cone  cells  are  their 
axones.  These  cells  constitute  the  first  or  distal  optic  neurone. 

The  bipolar  cells  (Fig.  506,  e),  which  with  their  processes  constitute  the 
middle  or  second  optic  neurone,  also  develop  from  cells  of  the  nuclear  layer 


584 


TEXT-BOOK  OF  EMBRYOLOGY. 


and  are  probably  bipolar  at  the  time  that  the  rod  and  cone  cells  are  in  the 
unipolar  condition.  Reference  to  the  two  bipolar  cells  shown  in  Fig.  506,  e,  e, 
shows  that  at  this  stage  in  their  development  their  outwardly  directed  processes 
extend  to  the  outer  limiting  membrane.  These  processes  must  either  actually 
shorten  or  else  fail  to  grow  in  length  proportionately  as  the  retina  increases  in 
thickness,  for  in  the  mature  retina  they  end  in  relation  with  the  centrally 
(inwardly)  directed  processes  (axones)  of  the  rod  and  cone  cells.  According  as 
they  are  in  relation  with  rod  cells  or  cone  cells,  they  are  known  as  rod  bipolars 
or  cone  bipolars.  The  retinal  layer  in  which  the  axones  of  the  rod  and  cone 

Inner  limiting  membrane 


Layer  of  nerve  fibe  rs 


Layer  of  nerve  cells 


Inner  molecular  layer 


<  horizontal  cells 

Inner  nuclear  layer  <  bipolar  cells 
(.  amacrine  cells 


Outer  molecular  layer 
Outer  nuclear  layer 

Outer  limiting  membrane 
Layer  of  rods  and  cones 


Layer  of  pigmented  epithelium 

FIG.  508. — Vertical  section  through  retina  of  a  five  and  one-half  months'  human  embryo. 

Modified  from  Lange. 

cells  and  the  dendrites  of  the  rod  and  cone  bipolars  intermingle  is  the  outer 
molecular  layer  of  the  adult  retina.  It  is  first  distinctly  recognizable  as  a  mo- 
lecular layer  about  the  end  of  the  fifth  month  (Fig.  508). 

The  development  of  the  outer  molecular  layer  separates  the  originally  single 
nuclear  layer  into  two  layers,  an  outer  composed  of  the  nuclei  of  the  rod  and  cone 
cells  and  an  inner  composed  of  the  nucleated  bodies  of  the  rod  and  cone 
bipolars,  of  the  horizontal  cells  (Fig.  506,  g)  and  of  the  amacrine  cells  (Fig.  506, 
/  and  i),  all  of  which  can  be  recognized  in  Golgi  specimens  by  the  end  of  the 
seventh  month.  The  rod  and  cone  bipolars  and  probably  most  of  the  other 
cells  of  the  inner  nuclear  layer  send  their  axones  centrally  to  lie  in  contact  with 
the  dendrites  and  bodies  of  the  ganglion  cells, 


THE  ORGANS   OF  SPECIAL  SENSE.  585 

With  the  development  of  the  cells  of  the  inner  nuclear  layer  and  their  proc- 
esses, there  differentiates  the  inner  molecular  layer  which  separates  the  inner 
nuclear  layer  and  the  layer  of  ganglion  cells.  It  consists  mainly  of  ramifica- 
tions of  the  dendrites  and  axones  of  cells  the  bodies  of  which  lie  in  the  inner 
nuclear  layer  and  in  the  layer  of  ganglion  cells.  (Fig.  508.) 

The  Chorioid  and  Sclera. — These  develop  wholly  from  the  mesoderm. 
The  way  in  which  the  mesoderm  grows  in  between  the  lens  and  the  surface  and 
surrounds  the  optic  cup  has  been  described  (p.  576).  That  part  of  the  meso- 
derm lying  immediately  external  to  the  retina  develops  very  early  a  close- 
meshed  capillary  network.  This  appears  before  there  is  any  definitely  limited 
sclera  and  may  be  considered  the  anlage  of  the  chorioid.  Somewhat  later  the 
mesoderm  which  lies  just  to  the  outside  of  the  chorioid  takes  definite  shape  as  the 
external  fibrous  tunic  of  the  eye  or  sclera. 

The  Vitreous. — The  manner  in  which  the  vitreous  humor  is  formed  has 
been  the  subject  of  much  controversy  and  remains  still  undetermined.  As 
already  noted  in  describing  the  development  of  the  lens  (p.  595),  the  latter  is  at 
first  in  direct  contact  with  the  inner  layer  of  the  retina  (Fig.  504).  The  lens  and 
the  retina  separate  as  the  vitreous  forms  between  them.  During  the  develop- 
ment of  the  lens  the  arteria  centralis  retinae  does  not  stop,  as  in  the  adult, 
with  its  retinal  branches,  but  continues  across  the  optic  cup  as  the  hyaloid 
artery  to  end  in  the  vessels  of  the  tunica  vasculosa  lends.  Some  investigators 
consider  the  vitreous  a  transudate  from  these  blood  vessels.  As  the  chorioidal 
fissure  closes,  some  mesodermic  tissue  is  enclosed  with  the  artery,  and  some 
investigators  consider  the  vitreous  a  derivative  of  this  mesoderm.  In  Birds 
the  formation  of  the  vitreous  humor  begins  before  either  mesoderm  or  blood 
vessels  have  penetrated  the  optic  cup,  and  Rabl  suggests  that  the  vitreous  may 
be  a  secretion  of  the  retinal  cells.  Bonnet  describes  a  double  origin  of  the 
vitreous,  differentiating  between  a  retinal  vitreous  and  a  mesoderm  vitreous. 
According  to  Bonnet,  the  primary  vitreous  body  begins  its  formation  before  the 
closure  of  the  chorioidal  fissure.  This  primary  vitreous  appears  at  the  time 
of  formation  of  the  optic  cup,  is  a  fibrillated  secretion  of  the  retinal  cells,  and 
fills  in  the  vitreous  space  with  a  feltwork  of  fine  fibrils.  With  the  formation  of 
the  optic  cup  and  the  closure  of  the  chorioidal  fissure  this  type  of  vitreous  forma- 
tion ceases  and  a  secondary  vitreous  body  formation  takes  place  from  the  cells 
of  the  pars  ciliaris  retinas.  This  is  also  fibrillated  and  there  develops  at  this 
time  the  so-called  hyaloid  membrane  which  closely  invests  the  vitreous.  Among 
the  fibers  of  the  vitreous  body  appears  the  vitreous  humor.  Up  to  this  point  the 
vitreous  is  entirely  non-cellular.  There  next  grow  into  it  mesodermal  cells 
which  have  reached  the  vitreous  through  the  chorioidal  fissure  along  with  the 
hyaloid  artery.  To  what  extent  these  cells  are  used  up  in  the  formation  of  the 
blood  vessels  of  the  vitreous  and  to  what  extent  they  remain  as  connective  tissue 


586  TEXT-BOOK  OF  EMBRYOLOGY. 

cells  of  the  mature  vitreous  after  the  blood  vessels  have  degenerated  is  not 
known. 

As  already  noted,  the  vitreous  is  at  first  crossed  by  the  hyaloid  artery  which 
supplies  the  developing  lens  (p.  579).  As  lens  formation  becomes  less  active 
the  artery  becomes  less  important  and  by  the  end  of  the  third  month  begins  to 
atrophy.  At  birth  nothing  remains  of  it,  but  in  its  former  course  the  vitreous 
is  somewhat  more  fluid  than  elsewhere  and  this  is  known  as  the  hyaloid  canal 
(canal  of  Cloquet). 

The  Optic  Nerve. — Referring  to  the  description  of  the  optic  evagination  it 
will  be  recalled  that  the  optic  vesicle  maintains  its  connection  with  the  brain  by 
means  of  the  optic  stalk  (p.  574).  The  latter  is  hollow  and  connects  the  cavity 
of  the  optic  vesicle  with  the  cavity  of  the  brain.  When  the  invagination  of  the 
optic  vesicle  to  form  the  optic  cup  occurs  (p.  576,  Fig.  502),  the  invagination  is 
carried  along  the  posterior  surface  of  the  optic  stalk  toward  the  brain,  and  just 
as  the  invagination  of  the  optic  vesicle  results  in  the  obliteration  of  the  cavity 
of  the  vesicle,  so  the  invagination  of  the  optic  stalk  results  in  an  oblitera- 
tion of  its  lumen.  In  Mammals  the  invagination  of  the  optic  stalk  extends  only 
part  way  to  the  brain,  to  the  point  where  the  artery  enters.  The  chorioidal 
fissure  closes  about  the  seventh  week. 

The  optic  stalk  consists  of  supportive  elements  only,  and  serves  as  a  track 
along  which  nerve  fibers  extend  to  connect  the  retina  and  brain.  Nerve  fibers 
appear  in  the  optic  stalk  about  the  fifth  week.  They  appear  first  around  the 
periphery  and  apparently  crowd  the  neuroglia  nuclei  toward  the  center,  so  that 
the  stalk  at  this  stage  may  be  said  to  consist  of  a  mantle  layer  and  a  marginal 
layer,  apparently  analogous  to  these  layers  in  the  retina  and  brain.  The  nerve 
fibers  gradually  invade  the  entire  stalk  so  that  by  the  end  of  the  third  month  the 
stalk  has  become  transformed  into  the  optic  nerve  among  the  fibers  of  which  the 
original  supportive  elements  of  the  stalk  are  still  represented  by  neuroglia  cells. 

Much  difference  of  opinion  has  existed  in  regard  to  the  origin  of  the  optic 
nerve  fibers,  whether  they  are  processes  of  retinal  cells  which  end  in  the  brain 
or  processes  of  brain  cells  which  end  in  the  retina.  It  is  now  quite  generally 
accepted  that  most  of  the  fibers  of  the  optic  nerve  are  the  axones  of  neurones  the 
cell  bodies  of  which  are  situated  in  the  ganglion  cell  layer  of  the  retina.  These 
axones  pass  centrally  into  the  layer  of  nerve  fibers,  which  they  form,  and  con- 
verge toward  the  optic  nerve.  Through  the  latter  they  pass  to  their  terminations 
in  the  external  geniculate  bodies,  optic  thalami  and  anterior  corpora  quadri- 
gemina.  According  to  Cajal  and  others,  some  centrifugal  fibers  are  present  in 
the  optic  nerve.  These  are  processes  of  cells  situated  in  the  above-mentioned 
nuclei,  and  terminate  in  the  retina.  They  are  fewer  in  number  and  of  later 
development  than  the  centripetal  fibers. 

As  the  mesodermic  anlagen  of  the  chorioid  and  sclera  are  present  before 


THE   ORGANS   OF  SPECIAL  SENSE.  587 

the  nerve  fibers  begin  to  grow  into  the  optic  stalk,  the  fibers  must  pass  through 
these  two  coats  in  their  exit  from  the  eye.  There  results  the  fenestrated  cross- 
ing of  the  optic  nerve  by  these  two  coats,  known  as  the  lamina  cribrosa. 

The  optic  nerve  fibers  are  medullated  but  have  no  neurilemmae.  They  are 
supported  by  neuroglia.  The  connective  tissue  sheaths  which  enclose  the  optic 
nerve  are  direct  extensions  of  the  meninges.  These  structural  peculiarities 
accord  with  the  peculiarities  already  described  in  the  development  of  the 
nerve.  Attention  has  been  called  to  the  fact  (p.  573)  that  just  as  the  retina 
should  be  considered  a  modified  and  displaced  portion  of  the  central  nervous 
system — of  brain  cortex — so  the  optic  nerve  should  be  considered  not  as  a 
peripheral  nerve,  but  as  analogous  to  a  central  nervous  system  fiber  tract. 

The  Ciliary  Body,  Iris,  Cornea,  Anterior  Chamber. — Anteriorly  where 
they  come  into  relation  with  the  lens  and  are  so  arranged  as  to  admit  light  to  the 
retina,  all  three  coats  of  the  eye  are  extensively  modified.  Thus  the  retina  is 
continued  anteriorly  as  the  pars  ciliaris  retinae  and  pars  iridica  retinas,  the 
chorioid  as  the  stroma  of  the  ciliary  body  and  iris,  the  sclera  as  the  cornea. 

THE  CILIARY  BODY  AND  IRIS. — Both  primary  retinal  layers  (the  two  layers 
of  the  optic  cup)  are  continued  anteriorly  as  the  non-nervous  retinal  layer 
of  the  ciliary  body  and  iris.  The  outer  pigmented  layer  consists  at  first  of 
several  layers  of  pigmented  cells,  but  later  becomes  reduced  to  a  single  layer 
of  pigmented  cells  which  do  not,  however,  possess  pigmented  processes  extend- 
ing inward  as  do  the  analogous  cells  of  the  nervous  retina.  The  abrupt  tran- 
sition at  the  ora  serrata  where  the  thick  pars  optica  retinas  passes  over  into  the 
pars  ciliaris  retinas  has  been  mentioned  (p.  580).  The  inner  layer  of  the  primi- 
tive retina  (optic  cup)  extends  over  the  ciliary  body  and  iris  as  a  single  layer  of 
cells.  These  remain  non-pigmented  over  the  ciliary  body,  but  over  the  iris 
acquire  pigment  so  that  the  two  layers  form  the  pigmented  layer  of  the  iris. 

The  mesodermic  tissue  which  forms  the  stroma  of  the  ciliary  body  and  iris 
is  derived  from  the  mesoderm  lying  between  the  lens  and  the  surface  ectoderm. 
This  separates  into  two  layers  enclosing  between  them  the  anterior  chamber  of 
the  eye,  and  it  is  from  the  posterior  of  these  two  layers  that  mesodermic  tissue 
extends  into  the  ciliary  body  and  iris.  It  is  continuous  with  the  mesoderm  of 
the  tunica  vasculosa  lentis.  During  the  fourth  month  the  ciliary  body  under- 
goes foldings  to  form  the  ciliary  processes.  These  foldings  at  first  involve 
also  the  iris,  but  the  iris  folds  soon  (end  of  fifth  month)  disappear,  while  the 
ciliary  processes  become  more  prominent. 

Of  the  smooth  muscle  tissue  found  in  the  ciliary  body  and  iris,  the  dilator 
and  contractor  pupillae  are,  according  to  Bonnet,  derived  from  the  cells  of  the 
pigmented  layer  of  the  retina,  i.e.,  from  ectoderm.  The  ciliary  muscle,  on  the 
other  hand,  develops  from  mesoderm.  These  muscles  become  well  developed 
during  the  seventh  month. 


588  TEXT-BOOK  OF  EMBRYOLOGY. 

The  suspensory  ligament  of  the  lens,  or  zonula  Zinnii,  first  appears  about  the 
end  of  the  fourth  month.  By  some  the  fibers  of  the  suspensory  ligament 
are  believed  to  differentiate  from  the  vitreous,  by  others  they  are  considered  as 
derived  from  the  pars  ciliaris  retinas.  Spaces  among  the  fibers  of  the  ligament 
enlarge  and  coalesce  to  form  the  canal  of  Petit. 

THE  CORNEA. — The  way  in  which  the  mesoderm  grows  in  between  the  lens 
vesicle  and  the  surface  ectoderm  has  been  described  (p.  576).  This  mesoderm 
forms  a  thin  almost  homogeneous  layer  containing  very  few  cells.  Later  that 
part  of  the  layer  which  lies  against  the  lens  becomes  more  cellular  and  vascular, 
so  that  it  is  possible  to  distinguish  between  an  outer  homogeneous  non- vascular 
layer  and  an  inner  cellular  vascular  layer.  The  former  is  the  anlage  of  the 
cornea.  Between  the  two  layers  vacuoles  appear  and  coalesce  to  form  the 
anterior  chamber  of  the  eye  or  cavity  of  the  aqueous  humor.  Subsequent 
growth  of  the  iris  subdivides  this  chamber  into  an  anterior  and  a  posterior 
portion.  The  chamber  separates  the  cornea  from  the  pupillary  membrane 
portion  of  the  tunica  vasculosa  lentis.  Bounding  the  chamber  anteriorly  and 
so  forming  the  posterior  layer  of  the  cornea  there  develops  a  single  layer  of 
flat  cells,  the  so-called  "endothelium"  of  Descemet.  Over  the  surface  of  the 
cornea  the  ectoderm  remains  and  gives  rise  to  a  stratified  squamous  epithelium 
four  to  eight  cells  thick,  the  anterior  corneal  epithelium.  Just  beneath  the 
epithelium  a  layer  of  corneal  tissue  retains  its  original  homogeneous  character 
and  forms  the  anterior  elastic  membrane  or  membrane  of  Bowman.  The 
posterior  elastic  membrane  or  membrane  of  Descemet  is  usually  considered  a 
cuticular  derivative  of  the  ''endothelium."  Throughout  the  rest  of  the  cornea 
— substantia  propria  cornea — cells  develop,  either  by  proliferation  of  the 
few  cells  originally  present  or  from  cells  which  grow  in  from  the  surrounding 
cellular  mesoderm,  and  become  arranged  parallel  to  the  surface  as  the  fixed 
connective  cells  of  the  cornea. 

The  Eyelids. — After  the  lens  vesicle  becomes  separated  from  the  surface 
ectoderm,  the  latter  folds  over  above  and  below  to  form  the  first  rudiments 
of  the  upper  and  lower  eyelids.  Each  fold  consists  of  a  core  of  mesoderm  and 
a  covering  of  ectoderm.  From  the  mesoderm  develop  the  connective  tissue 
elements  of  the  lids  including  the  tarsal  cartilage.  From  the  ectoderm  develop 
the  epithelial  structures  of  the  lids,  the  epidermis,  the  eyelashes  and  the  glands. 
The  edges  of  the  lids  gradually  approach  each  other  and  about  the  beginning 
of  the  third  month  the  epithelium  of  the  upper  lid  becomes  adherent  to  that 
of  the  lower,  thus  completely  shutting  in  the  eyeball.  This  condition  obtains 
until  just  before  birth. 

The  eyelashes  develop  in  the  same  manner  as  other  hairs  (p.  447). 

The  Meibomian  glands,  glands  of  Moll  and  the  lacrymal  glands  develop, 
during  the  period  the  lids  are  adherent,  as  solid  cords  of  ectoderm  which  grow 


THE   ORGANS   OF  SPECIAL  SENSE.  589 

into  the  underlying  mesoderm  where  they  ramify  to  form  the  ducts  and  tubules. 
The  anlagen  of  the  ducts  and  tubules  of  these  glands  are  thus  at  first  solid  cords 
of  cells,  their  lumina  being  formed  later  by  a  breaking  down  of  the  central  cells 
of  the  cords. 

At  the  inner  angle  of  the  conjunctiva  there  develops  beneath  the  eyelid 
folds  a  third  much  smaller  fold.  This  becomes  the  plica  semilunaris  which 
in  man  is  a  rudimentary  structure,  but  in  many  of  the  lower  Vertebrates, 
especially  Birds,  forms  a  distinct  third  eyelid,  the  so-called  nictitating  mem- 
brane. A  few  hair  follicles  and  sebaceous  glands  develop  in  a  portion  of  this 
fold  forming  the  lacrymal  caruncle. 

The  Lacrymal  Duct.  At  a  certain  stage  in  development,  a  groove  bounded 
by  the  maxillary  process  and  the  lateral  nasal  process  extends  from  the  eye  to 
the  nose  (Fig.  136).  This  is  known  as  the  naso-optic  furrow.  The  ectoderm 
(epithelium)  lying  along  the  bottom  of  this  groove  thickens  about  the  sixth 
week  and  forms  a  solid  cord  of  cells.  As  development  proceeds  and  the  parts 
close  in,  this  cord  of  ectoderm  becomes  enclosed  within  the  mesoderm,  excepting 
at  its  ends  where  it  remains  connected  with  the  surface  ectoderm  of  the  eye  and 
nose,  respectively.  By  a  breaking  down  of  the  central  cells  of  this  cord  a  lumen 
is  formed  and  the  cord  becomes  a  tube,  the  lacrymal  duct.  The  primary  con- 
nection of  the  lacrymal  duct  is  with  the  upper  lid,  but  while  the  lumen  is  being 
formed  an  offshoot  grows  out  to  the  under  eyelid  to  form  the  inferior  branch 
of  the  lacrymal  duct. 

THE  NOSE. 

The  anlage  of  the  organ  of  smell  is  apparent  in  human  embryos  of  about 
three  weeks  as  two  thickenings  of  the  ectoderm,  one  on  each  side  of  the  naso- 
frontal  process.  To  these  thickenings  the  term  olfactory  placodes  has  been 
applied  (Kupffer).  A  little  later  (in  embryos  of  about  four  weeks),  the  placodes 
become  depressed  below  the  surface,  the  depressions  themselves  being  the 
nasal  pits  or  fosses  (see  p.  152;  also  Fig.  123).  The  placodes,  which  are 
destined  to  give  rise  to  the  sensory  epithelium,  thus  come  into  closer  relation 
with  the  olfactory  lobes  of  the  brain  (rhinencephalon)  which  represent  out- 
growths of  the  fore-brain  (telencephalon)  (see  p.  508) . 

As  described  in  connection  with  the  development  of  the  face,  the  lateral 
nasal  process  arises  on  the  lateral  side,  the  medial  nasal  process  on  the  medial 
side,  of  each  nasal  pit  (p.  152  el  seq.;  also  Fig.  134).  Of  these  processes,  the 
lateral  is  destined  to  give  rise  to  the  lateral  nasal  wall  and  the  wing  of  the  nose, 
the  medial  to  a  part  of  the  nasal  septum  (see  p.  152).  As  development  pro- 
ceeds, the  epithelium  (ectoderm)  of  the  nasal  fossae  grows  still  deeper  into  the 
subjacent  mesoderm,  the  fossae  thus  becoming  converted  into  the  nasal  sacs, 
which  He  above  the  oral  cavity.  According  to  Hochstetter  and  Peter,  the 


590  TEXT-BOOK  OF  EMBRYOLOGY. 

nasal  sacs  are  not  at  first  in  communication  with  the  oral  cavity,  but  lie  above, 
and  are  separated  from  it  by  a  plate  of  tissue  which  gradually  becomes  thinned 
out  along  the  deeper  part  of  the  sacs  to  form  the  bucco-nasal  membrane  (Hoch- 
stetter).  Later  (in  embryos  of  15  mm.),  the  bucco-nasal  membrane  ruptures 
and  the  deep  ends  of  the  sacs  thus  come  to  open  into  the  mouth  cavity,  the 
openings  being  known  as  the  primitive  choanen.  In  front  of  the  primitive 
choanen,  the  nasal  passages  (formerly  the  nasal  sacs)  are  separated  from 
the  mouth  cavity  by  a  plate  of  tissue,  known  as  the  primitive  palate  (Fig.  509). 
The  latter  is  produced  by  the  fusion  of  the  maxillary  process  with  the  lateral 
and  medial  nasal  processes  (see  p.  152),  the  outer  nares  thus  being  somewhat 
separated  from  the  border  of  the  mouth. 

The  further  separation  of  the  nasal  passages  from  the  oval  cavity  has  been 
described  in  connection  with  the  development  of  the  mouth  (p.  318)  and  the 


Lateral  nasal  process 

Outer  nasal  opening 

Maxillary  process 

Eye 

Primitive  choanen 

Palatine  process 


FIG.  509. — From  a  model  of  the  anterior  part  of  the  head  of  a  15  mm.  human  embryo.     The  lower 
jaws  (mandibular  processes)  have  been  removed.     Peter. 

development  of  the  palatine  processes  of  the  maxillas.  It  may  be  repeated 
briefly,  however,  that  from  each  maxillary  process  a  horizontal  extension  grows 
across  between  the  oral  and  nasal  cavities  until  it  meets  and  fuses  with  its  fellow 
of  the  opposite  side  and  with  the  nasal  septum  in  the  medial  line,  thus  forming 
the  palate  which  is  continuous  with  the  primitive  palate  mentioned  above. 
(See  Figs.  178  and  510.)  In  this  way  the  nasal  cavities  or  chambers  become 
separated  from  the  oral  cavity,  but  remain  in  communication  with  the  pharyn- 
geal  cavity  through  the  posterior  nares. 

The  nasal  cavities  increase  enormously  in  size  and  the  epithelial  surface  in 
extent,  owing  to  (i)  the  formation  of  the  palate  alluded  to  above,  (2)  the  develop- 
ment of  the  nasal  concha  which  has  been  described  on  page  196,  and  (3)  the 
development  of  accessory  cavities — maxillary,  frontal  and  sphenoidal  sinuses, 
which  represent  evaginations,  so  to  speak,  from  the  nasal  cavities. 

Probably  correlated  with  the  above-mentioned  increase  in  extent  of  the 
nasal  chambers  is  the  fact  that  in  lung-breathing  Vertebrates  the  chambers 


THE   ORGANS   OF  SPECIAL  SENSE. 


591 


have  acquired  a  secondary  function.  In  these  forms  the  nose  is  not  only  an 
apparatus  for  receiving  olfactory  stimuli,  but  also  serves  to  convey  air  to  and 
from  the  lungs;  it  is  in  a  sense  a  respiratory  atrium.  The  sensory  epithelium 
which  the  olfactory  nerves  supply  is  limited  to  relatively  small  areas  in  the  supe- 
rior conchae  and  nasal  septum.  Stratified  columnar  ciliated  epithelium  lines  all 
other  parts  of  the  cavities. 

Studies  on  the  development  of  the  olfactory  nerve  have  led  to  diverse 
opinions,  but  the  investigations  of  His  and  Disse  go  to  show  that  the  fibers 
are  processes  of  cells  derived  from  the  thickened  ectoderm  or  olfactory  placodes. 
In  human  embryos  of  about  four  weeks  some  of  the  cells  in  the  upper  part  of 
the  nasal  fossa  become  modified  to  form  the  neuro-epithelium.  From  the 


Jacobson's  organ 
Inferior  concha 

Jacobson's  cartilage 


Palatine  process 


Nasal  septum 


Nasal  cavity 


Oral  cavity 


FIG.  510. — From  a  section  through  the  head  of  a  human  embryo  of  28  mm.,  showing  the  nasal 
septum,  the  nasal  cavities,  the  oral  cavity,  and  the  palatine  processes.     Peter. 

peripheral  pole  of  each  cell  a  short  slender  process  grows  out  to  the  surface  of 
the  epithelium.  From  the  opposite  pole  a  slender  process  (the  axone)  grows 
centrally  until  it  penetrates  the  olfactory  lobe,  where  it  ends  in  contact  with  the 
dendrites  of  the  first  central  neurone  of  the  olfactory  tract.  Most  of  these  cells 
remain  in  the  epithelial  layer,  but  a  few  wander  into  the  subjacent  mesoderm 
and  become  bipolar  cells  which  resemble  the  bipolar  cells  of  the  embryonic 
posterior  root  ganglia  (p.  509).  Other  epithelial  cells  of  the  nasal  fossa  are 
converted  into  the  sustentacular  cells  of  the  olfactory  areas. 

Jacobson's  organ  arises  at  the  beginning  of  the  third  month  as  a  small  out- 
pocketing  of  the  epithelium  on  the  lower  anterior  part  of  the  nasal  septum 
(Fig.  510).  This  evagination  grows  backward  as  a  slender  sac  along  the  nasal 
septum  for  a  distance  of  several  millimeters  and  ends  blindly.  In  the  adult 
the  sac  degenerates  and  often  disappears.  In  some  of  the  lower  Mammals 
38 


592  TEXT-BOOK  OF  EMBRYOLOGY. 

Jacobson's  organ  develops  to  a  greater  degree,  and  some  of  the  epithelial  cells 
send  out  processes  which  pass  to  the  olfactory  lobes. 

THE  EAR. 

The  ear  of  higher  Vertebrates  consists  of  three  parts — the  internal,  middle, 
and  external.  Of  these,  the  internal  is  the  sensory  portion  proper  and,  so  far 
as  the  epithelial  elements  are  concerned,  is  of  ectodermal  origin,  but  secondarily 
becomes  embedded  in  the  subjacent  mesoderm.  It  constitutes  a  complicated 
and  highly  specialized  structure  for  the  reception  of  certain  stimuli  that  are  to  be 
conveyed  to  the  central  nervous  system.  From  a  functional  standpoint  it  may 
be  divided  into  the  portion  composed  of  the  semicircular  canals  and  their  ap- 
pendages, which  is  concerned  in  receiving  and  transmitting  stimuli  destined 


Rh.  br. 


!•  Co.  gang. 


FIG.  511. — Half  of  a  transverse  section  through  the  region  of  the  developing  ear  of  a  sheep 

embryo  of  13  mm.     Bottcher. 

And.  ves.,  Auditory  vesicle;  Co.   gang.,    cochlear  ganglion;  End.  ap.,  endolymphatic 
appendage;  Rh.br.,  rhombic  brain. 

for  the  static  and  equilibration  centers  in  the  central  nervous  system,  and  the 
cochlear  portion,  which  is  concerned  in  receiving  and  transmitting  auditory 
stimuli.  The  middle  and  outer  ear  represent  modified  portions  of  the  most 
cranial  of  the  branchial  arches  and  grooves,  and  constitute  an  apparatus  for 
conducting  sound  waves  to  the  cochlear  portion  of  the  inner  ear. 

The  Inner  Ear. — In  embryos  of  2  to  4  mm.,  the  ectoderm  becomes  some- 
what thickened  over  a  small  area  lateral  to  the  still  open  neural  groove  in  the 
region  of  the  future  hind-brain.  This  thickening  is  often  spoken  of  as  the 
auditory  placode  (see  p.  506).  Owing  to  more  rapid  growth  of  the  cells  in  the 
deeper  layers  of  the  placode,  it  soon  becomes  converted  into  a  cup-shaped 
depression  which  is  known  as  the  auditory  pit.  The  edges  of  the  pit  fold 
in  and  fuse  and  the  pit  thus  becomes  the  auditory  vesicle  (otocyst),  which 
finally  becomes  constricted  from  the  parent  ectoderm  and  lies  free  in  the  sub- 
jacent mesoderm  (Fig.  511). 


THE   ORGANS   OF  SPECIAL  SENSE.  593 

At  this  stage  (embryos  of  4  to  5  mm.)  the  auditory  vesicle  is  an  oval  or 
spherical  sac  the  wall  of  which  consists  of  two  or  three  layers  of  undifferen- 
tiated  epithelial  cells.  It  lies  against  the  neural  tube  and  is  connected  with  the 
latter  by  the  acoustic  ganglion  (Fig.  512,  a).  About  the  same  time  an  evagina- 
tion  appears  on  the  dorsal  side  of  the  auditory  vesicle,  forming  the  anlage  of  the 
endolymphatic  appendage  (Fig.  512,  a,  b,  c).  The  evagination  continues  to 
elongate  and  comes  to  form  a  club-shaped  structure,  the  distal  end  of  which 
becomes  flattened  to  form  the  endolymphatic  sac,  the  narrower  proximal  portion 
constituting  the  endolymphatic  duct  (Fig.  512  a-n).  The  epithelium,  which  at 
first  consisted  of  two  or  three  layers  of  cells,  becomes  reduced  to  a  single  layer. 
In  the  chick  the  endolymphatic  appendage  is  formed  out  of  the  original  union 
between  the  ectoderm  and  the  auditory  vesicle  (Keibel,  Krause).  In  Reptiles 
and  Amphibia  (Peter,  Krause)  and  in  man  (Streeter),  on  the  other  hand,  this 
appendage  develops  independently  of  the  union,  appearing  on  the  dorsal  side  of 
the  seam  of  closure  in  the  auditory  vesicle. 

In  embryos  of  about  6  mm.  the  auditory  vesicle  (apart  from  the  endolymph- 
atic appendage)  becomes  differentiated  into  two  portions  or  pouches — a  bulging, 
triangular  one  above,  which  is  connected  with  the  endolymphatic  appendage, 
and  a  more  flattened  one  below.  The  former  is  the  vestibular  pouch,  the  latter 
the  cochlear  pouch  (Fig.  512,  b-f).  Between  the  two  is  a  portion  of  the  vesicle 
which  is  destined  to  give  rise  to  the  saccule  and  utricle,  and  which  may  be  called 
the  atrium  (Streeter).  Properly  speaking,  the  atrium  is  a  division  of  the 
vestibular  pouch.  The  cochlear  pouch  is  phylogenetically  a  secondary  diver- 
ticulum  which  develops  from  the  atrium,  appearing  first  in  the  lowest  land- 
inhabiting  Vertebrates  (Amphibia). 

As  mentioned  above,  the  vestibular  pouch  early  assumes  the  form  of  a 
triangle,  with  the  apex  toward  the  endolymphatic  appendage.  The  three 
borders  of  the  triangle  form  the  anlagen  of  the  semicircular  canals  and  bear  the 
same  interrelation  as  the  latter.  At  the  same  time  a  vertical  groove  (the  lateral 
groove)  appears  between  the  anlage  of  the  posterior  canal  and  the  posterior  end 
of  the  lateral  canal  (Fig.  512,  b,  d). 

The  formation  of  the  semicircular  canals  is  shown  in  Fig.  512,  g-k.  The 
edges  of  the  triangular  vestibular  pouch  expand  and  become  more  or  less 
crescentic  in  shape.  The  two  walls  in  the  concavity  of  each  crescent  come 
together  and  then  break  away  (Fig.  512,  g,  j,  absorp. focus),  thus  leaving  the  rim 
of  the  crescent  as  a  canal  attached  at  its  two  ends  to  the  utricle.  The  breaking 
away  affects  first  the  superior,  then  the  posterior,  and  finally  the  lateral  canal. 
During  these  gross  changes  the  epithelium  becomes  reduced  to  a  single  layer 
of  cells. 

At  one  end  of  each  canal  an  enlargement  appears  to  form  the  ampulla,  as 
shown  in  Fig.  512,  /,  m,  n,  and  Fig.  513,  a,  b,  c. 


594 


TEXT-BOOK  OF  EMBRYOLOGY. 


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THE   ORGANS  OF  SPECIAL  SENSE. 


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596  TEXT-BOOK  OF  EMBRYOLOGY. 

The  utricle  and  saccule  represent  divisions  of  the  portion  of  the  vestibular  sac 
which  is  known  as  the  atrium,  and  into  which  the  endolymphatic  appendage 
and  cochlea  open  (see  p.  593).  In  embryos  of  about  20  mm.  a  horizontal  con- 
striction begins  to  divide  the  atrium  into  an  upper  utricular  portion,  into  which 
the  semicircular  canals  open,  and  a  lower  saccular  portion  (Fig.  512,  /,  m). 
The  constriction  begins  on  the  side  opposite  the  endolymphatic  appendage  and 
gradually  extends  across  the  atrium  until  it  finally  divides  the  opening  of  the 
endolymphatic  appendage  into  two  parts  (Fig.  513,  a,  b,  c).  One  of  these 
parts  opens  into  the  utricle,  the  other  into  the  saccule,  the  two  parts  together 
constituting  the  utriculo saccular  duct. 

As  stated  before,  the  two-  or  three-layered  epithelium  of  the  earlier  stages 
becomes  reduced  to  a  single  layer.  The  cells  of  this  layer  are  low  cuboidal, 
with  the  exception  of  those  over  small  areas  in  the  ampullae,  in  the  saccule,  and 
in  the  utricle.  Over  an  elongated  area  in  each  ampulla  (crista  ampullaris),  a 
round  area  in  the  saccule  and  another  in  the  utricle  (macula  acustica),  the 
epithelium  becomes  high  columnar,  some  of  the  cells  developing  cilia  on  their 
free  borders  ("hair  cells,"  neuro-epithelium) ,  the  others  becoming  the  susten- 
tacular  cells.  These  areas  are  the  end-organs  of  the  vestibular  nerve  (see  p.  506) . 

As  already  mentioned,  the  cochlear  pouch  appears  as  an  outgrowth  from  the 
lower  side  of  the  atrium  (see  also  Fig.  512,  b-f).  The  pouch  becomes  somewhat 
flattened,  and,  as  it  continues  to  grow  in  length,  becomes  coiled  like  a  snail- 
shell  (Fig.  512,  g-n;  Fig.  513,  a-c}.  This  first  formed  coiled  structure  is  the 
cochlear  duct,  or  scala  media.  At  the  same  time,  it  becomes  distinctly  marked 
off  from  the  lower  part  of  the  atrium  (now  the  saccule)  by  a  constriction,  the 
constricted  portion  forming  the  ductus  reuniens  (Fig.  512,  l-n;  Fig  513,  a-c). 

All  the  structures  thus  far  considered  are  at  first  closely  invested  by  meso- 
derm.  Later,  this  portion  of  the  mesoderm  gives  rise  to  special  tissues,  and,  in 
the  region  of  the  cochlear  duct,  to  the  scala  vestibuli  and  scala  tympani.  The 
cells  immediately  around  the  vesicle  proliferate  and  a  dense  fibrous  layer  is 
formed;  outside  of  this  fibrous  layer  the  tissue  becomes  gelatinous;  outside  of 
this  again  another  fibrous  layer  is  formed,  around  which  cartilage  develops. 
The  inner  fibrous  layer  gives  rise  to  the  connective  tissue  that  supports  the 
epithelial  lining  of  the  vesicle.  The  gelatinous  layer  degenerates  to  form  a 
fluid  known  as  the  perilymph,  the  space  containing  the  fluid  being  the  perilymph- 
atic  space.  The  outer  fibrous  layer  becomes  the  perichondrium — later  the 
periosteum  when  the  cartilage  is  replaced  by  the  petrous  portion  of  the  tem- 
poral bone. 

In  the  cochlear  region  the  conditions  are  somewhat  modified.  Here  the 
gelatinous  layer  does  not  form  a  complete  covering  for  the  cochlear  duct,  but  is 
interrupted  along  two  lines,  (i)  Laterally  the  fibrous  layer  lying  next  the 
cochlear  duct  is  fused  with  the  perichondrium  (outer  fibrous  layer)  (Fig.  514). 


THE   ORGANS   OF  SPECIAL  SENSE. 


597 


(2)  Medially  the  inner  fibrous  layer  is  fused  with  the  perichondrium  of  a  shelf-like 
process  of  cartilage  which  later  ossifies  to  form  the  bony  spiral  lamina  (Fig. 
514).  By  these  two  partitions  the  cochlear  perilymphatic  space  is  separated 
into  two  spiral  compartments  which  communicate  only  at  the  apex  of  the 
cochlea.  The  larger  of  these  compartments,  the  scala  vestibuli,  communicates 
with  the  perilymphatic  space  around  the  utricle  and  saccule.  The  wall  separat- 
ing: the  scala  vestibuli  and  cochlear  duct  becomes  thinned  out  to  form  the 


Cochlear  duct 


Cartilage 

Scala  vestibuli 
(gelatinous  tissue) 


Cochlear  duct 

Cochlear  (spiral)  ganglion    jpi 

Coch.  nerve  to  organ  of  Corti 
Scala  tympani 
Cochlear  nerve 
Fibrous  con.  tis.    — j~ 
Connective  tissue  _| 

Scala  vestibuli  __£ 
Perichondrium 

Vestibular  membrane  _| 
Lat.  wall  of  coch.  duct 

Organ  of  Corti 


Scala  tympan    •! 


Cartilage 


FIG.  514 — Section  through  the  developing  cochlea  of  a  go  mm.  cat  embryo.     Bottcher. 


•uestibular  membrane  (of  Reissner).  The  smaller  compartment,  the  scala 
tympani,  remains  separated  from  the  cavity  of  the  middle  ear  by  a  thin  mem- 
brane which  closes  the  fenestra  cochlea  (rotunda).  In  the  wall  between  the 
scala  tympani  and  the  cochlear  duct  the  organ  of  Corti  develops  (see  below). 
A  membrane,  similar  to  that  closing  the  fenestra  cochleae,  occurs  between  the 
cavity  of  the  middle  ear  and  the  utricle,  closing  the  fenestra  vestibuli  (ovalis). 
As  alluded  to  above,  the  organ  of  Corti  develops  from  the  wall  of  the  cochlear 


598  TEXT-BOOK  OF  EMBRYOLOGY. 

duct  between  the  latter  and  the  scala  tympani  (Fig.  514).  The  epithelial  cells 
of  the  cochlear  duct  in  this  region  become  high  columnar  and  arranged  in  two 
ridges  which  extend  throughout  the  entire  length  of  the  duct.  The  cells  of  the 
ridge  nearer  the  axis  of  the  cochlea  give  rise  to  the  membrana  tectoria.  Whether 
this  is  accomplished  by  cuticular  secretion  of  the  cells  or  by  the  fusion  of  long 
hair-like  processes  that  grow  from  their  free  borders  is  not  known.  The  cells  of 
the  outer  ridge  become  differentiated  into  four  groups.  Those  of  the  outer 
group  (next  the  cells  that  give  rise  to  the  membrana  tectoria)  develop  into  the 
inner  hair  cells;  those  of  the  next  group  form  the  pillar  cells;  those  of  the  third 
group  differentiate  into  the  outer  hair  cells;  and  those  of  the  fourth  (outer) 
group  give  rise  to  Hensen's  cells.  The  hair  cells,  as  the  name  indicates,  develop 
delicate  hair-like  processes  on  their  free  borders,  and,  since  the  peripheral 
processes  of  the  spiral  (cochlear)  ganglion  cells  end  around  them,  are  con- 
sidered as  the  sensory  cells  of  the  cochlea,  or  auditory  receptors  (see  p.  506). 

THE  ACOUSTIC  NERVE. — The  acoustic  ganglionic  mass  is  at  first  closely 
associated  with  the  geniculate  ganglion  (ganglion  of  the  facial  (VII)  nerve) ,  the 
two  together  often  being  spoken  of  as  the  acustico-facialis  ganglion  (see  also 
p.  505).  This  lies  in  close  contact  with  the  anterior  wall  of  the  auditory  vesicle 
when  the  latter  is  first  constricted  from  the  ectoderm.  The  origin  of  the  gang- 
lion has  not  been  traced  in  Mammals,  but  in  cow  embryos  the  geniculate  has 
been  seen  to  be  connected  with  the  ectoderm  at  the  dorsal  end  of  the  first 
branchial  groove  (Froriep).  The  acoustic  ganglion  probably  belongs  to  the 
lateral  line  system  (Kupffer)  (see  also  p.  467). 

Although  the  geniculate  and  acoustic  ganglia  are  at  first  closely  associated, 
each  pursues  an  independent  course  of  development.  The  description  here 
will  be  confined  to  the  acoustic.  As  already  mentioned,  this  lies  in  close  apposi- 
tion to  the  side  of  the  neural  tube  and  the  auditory  vesicle  and  just  anterior  to 
the  latter  (Fig.  512,  a).  At  a  very  early  stage  (embryos  of  6-7  mm.),  the  mass 
shows  a  differentiation  into  two  parts — a  dorsal  one,  the  future  vestibular 
ganglion,  and  a  ventral  one,  the  future  cochlear  (spiral)  ganglion  (Fig.  512,  b,  c}. 
The  ganglion  cells  become  bipolar  (see  p.  506),  and,  as  is  peculiar  to  the  cells  of 
the  acoustic  ganglia,  remain  in  this  condition.  One  process  of  each  cell  grows 
centrally  to  form  a  root  fiber  of  the  acoustic  nerve,  which  terminates  in  contact 
with  dendrites  of  neurones  in  certain  nuclei  in  the  central  nervous  system.  The 
fibers  from  the  cells  of  the  vestibular  ganglion  form  the  vestibular  root,  those 
from  the  cells  of  the  cochlear  ganglion  form  the  cochlear  root.  The  other  proc- 
ess grows  peripherally  and  penetrates  the  wall  of  the  auditory  vesicle  to  enter 
into  relation  with  certain  cells  that  differentiate  from  the  epithelial  lining  of  the 
vesicle. 

The  peripheral  processes  of  the  vestibular  ganglion  cells  come  into  relation 
with  specialized  cells  (hair  cells)  in  the  ampullae  of  the  semicircular  canals 


THE   ORGANS   OF  SPECIAL  SENSE.  599 

(crista  ampullaris)  and  in  the  saccule  and  utricle  (macula  acustica)  (see 
p.  596).  The  nerve  itself  becomes  divided  into  certain  branches,  as  indicated 
in  the  following  table  (Streeter).  The  peripheral  terminations  of  the  various 
branches  are  indicated  in  parentheses.  Compare  with  Fig.  512,  /,  m,  n,  and 
Fig.  513,  a,  b,  c. 

{  ramus  ampul,  sup.  (crista  ampul.) 
pars  superior    j  ramus  ampul,  ext.  (crista  ampul.) 

(  ramus  recess,  utric.  (macula  acust.) 
N.  vestibularis        \ 

J  ramus  saccul.  (macula  acust.) 
pars  inferior     j  ramus  ampul,  (crista  ampul.) 

The  vestibular  ganglion  cells,  instead  of  remaining  in  a  compact  mass,  come 
to  form  two  fairly  distinct  masses  in  the  course  of  the  nerve  (Fig.  513,  a,  b,  c). 
One  of  these  apparently  is  connected  with  the  pars  inferior,  the  other  with  the 
pars  superior. 

The  cochlear  ganglion  cells  at  an  early  stage  become  closely  associated  with 
the  developing  cochlear  duct  and,  as  the  latter  forms  a  spiral,  are  carried  along 
with  it.  They  thus  come  to  form  an  elongated  group  of  cells  extending  through- 
out the  entire  length  of  the  cochlea  (whence  the  name,  spiral  ganglion)  (Fig. 
512,  j-n;  Fig.  513,  a-c).  Consequently,  the  peripheral  processes  of  these  cells, 
which  terminate  in  connection  with  the  hair  cells  of  the  organ  of  Corti,  are  com- 
paratively short.  The  central  processes  are  naturally  longer  and  form  the 
cochlear  nerve  root  which  is  twisted  like  a  rope  in  part  of  its  course  (Fig.  513,  c). 

The  Middle  Ear. — The  cavity  of  the  middle  ear  develops  from  the  upper 
(dorsal)  part  of  the  first  inner  branchial  groove.  The  epithelial  lining  of  the 
cavity  is  thus  of  course  derived  from  entoderm,  and  the  other  structures 
(auditory  ossicles,  etc.)  from  the  adjacent  mesoderm. 

It  has  been  stated  elsewhere  that  the  mesoderm  in  the  first  and  second 
branchial  arches  gives  rise,  among  other  things,  to  certain  skeletal  elements. 
In  the  first  arch  there  develops  a  rod  of  cartilage,  known  as  Meckel's  cartilage, 
which  extends  from  the  symphysis  of  the  lower  jaws  to  the  region  of  the  upper 
part  of  the  first  inner  branchial  groove  (p.  200;  Figs.  174,  177,  180).  The 
proximal  end  of  the  cartilage  becomes  constricted  to  form  two  masses  which 
constitute  the  anlagen  of  the  malleus  and  incus  (Figs.  173  and  174).  In  the 
second  arch  there  develops  a  rod  of  cartilage  which  forms  the  lesser  horn  of  the 
hyoid  bone,  the  stylohyoid  ligament,  and  the  styloid  process  (Figs.  174,  177, 
1 80) .  In  close  relation  to  the  dorsal  end  of  the  styloid  process,  in  the  mesoderm 
destined  to  give  rise  to  the  periotic  capsule,  a  mass  of  cartilage  appears  which 
is  destined  to  give  rise  to  the  stapes  (except  the  base?).  It  has  not  been  fully 
determined  whether  the  stapes  is  actually  a  derivative  of  the  cartilage  of  the 
second  arch  or  of  the  mesenchyme  near  its  dorsal  end.  It  has  been  suggested 


600  TEXT-BOOK  OF  EMBRYOLOGY. 

that  the  base  of  the  stapes  is  of  intramembranous  origin  and  that  the  rest  of  the 
bone  is  derived  from  the  cartilage  of  the  second  arch.  Its  close  association 
with  the  cartilage  of  the  second  arch  possibly  indicates  its  phylogenetic  origin 
from  the  latter. 

At  first  the  auditory  ossicles  are  embedded  in  the  mesoderm  dorsal  to  the 
first  inner  branchial  groove,  that  is,  dorsal  to  the  cavity  of  the  middle  ear.  As 
development  proceeds,  the  mesoderm  is  converted  into  a  spongy  tissue  which 
finally  degenerates.  At  the  same  time  the  ear  cavity  enlarges  and  wraps  itself, 
as  it  were,  around  the  ossicles.  The  latter  thus  come  to  lie  within  the  cavity 
of  the  tympanum,  but  are  covered  by  a  layer  of  epithelium  (entoderm)  which 
is  continuous  with  that  lining  the  cavity. 

Toward  the  end  of  fcetal  life,  outgrowths  from  the  cavity  of  the  tympanum 
begin  to  invade  the  temporal  bone.  This  process  continues  for  some  time 
after  birth  and  results  in  the  formation  of  cavities  within  the  mastoid  part  of 
the  temporal  bone.  These  cavities  are  the  mastoid  cells,  the  epithelial  lining 
of  which  is  continuous  with  that  of  the  tympanic  cavity. 

The  Eustachian  tube  represents  the  lower  (ventral)  portion  of  the  diver- 
ticulum  which  forms  the  cavity  of  the  tympanum.  In  other  words,  as  the 
dorsal  part  of  the  first  inner  branchial  groove  enlarges  to  form  the  cavity  of  the 
middle  ear,  the  narrow  part  of  the  groove,  just  ventral  to  the  cavity,  persists 
as  a  communication  between  the  latter  and  the  pharynx. 

The  Outer  Ear. — The  outer  ear  is  formed  from  the  dorsal  part  of  the  first 
outer  branchial  groove  and  the  adjacent  portions  of  the  first  and  second  arches 
(see  Fig.  123).  The  ventral  part  of  the  groove  flattens  out  and  disappears. 
The  dorsal  part  becomes  deeper  to  form  a  funnel-shaped  depression  (during 
the  second  month;  Fig.  126).  From  the  deeper  part  of  the  funnel  a  solid  mass 
of  ectoderm  grows  inward  until  it  comes  into  relation  with  the  mesoderm  im- 
mediately around  the  developing  cavity  of  the  tympanum,  or,  more  specifically, 
the  mesoderm  surrounding  the  handle  of  the  malleus.  Here  it  spreads  out 
into  a  disk-like  mass.  About  the  seventh  month,  the  disk  splits  into  two  layers. 
The  inner  layer,  which  is  separated  from  the  epithelium  of  the  middle  ear  by  a 
thin  sheet  of  mesoderm,  becomes  the  outer  layer  of  the  tympanum.  The 
tympanum  is  thus  composed  of  an  inner  (entodermal)  and  an  outer  (ectoder- 
mal)  layer,  with  a  small  amount  of  mesoderm  between.  From  its  mode  of 
development,  the  tympanum  may  be  considered  in  a  sense  as  the  wall  which 
separates  the  first  inner  from  the  first  outer  branchial  groove. 

The  split  in  the  ectodermal  disk  (see  above)  gradually  extends  outward, 
invading  the  solid  ectodermal  invagination  until  it  finally  unites  with  the 
bottom  of  the  funnel-shaped  depression  on  the  surface,  thus  forming  the 
external  auditory  meatus. 

The  external  ear  (or  auricle)  is  derived  from  the  portions  of  the  first  and 


THE  ORGANS   OF  SPECIAL  SENSE. 


601 


second  branchial  arches  surrounding  the  dorsal  part  of  the  first  outer  branchial 
groove  (see  Figs,  122,  123,  126,  127).  About  the  end  of  the  fourth  week,  the 
caudal  border  of  the  first  arch  exhibits  three  small  elevations  or  tubercles 
(Fig.  515,  At  1-3),  the  cranial  border  of  the  second  arch  the  same  number  (Fig. 
515,  A,  4-6).  A  groove,  extending  down  the  middle  of  the  second  arch,  marks 
off  a  ridge  (c)  lying  caudal  to  the  three  tubercles.  The  ventral  tubercle  (i)  of 
the  first  arch  gives  rise  to  the  Iragus.  The  middle  tubercle  (5)  of  the  second  arch 


f 


c 


FIG.  515. — Stages  in  the  development  of  the  external  ear  (auricle).  A,  Embryo  of  u  mm.;  B,  of 
13.6  mm.;  C,  of  15  mm.;  D,  foetus  at  the  beginning  of  the  3<d  month;  E,  foetus  of  8.5  cm.; 
F,  foetus  at  term.  For  explanation  of  numerals,  see  text.  His,  McMurrich. 

develops  into  the  antitragus .  The  middle  and  dorsal  tubercles  (2  and  3)  of 
the  first  arch  unite  with  the  ridge  (c)  on  the  second  arch  to  form  the  helix. 
The  dorsal  tubercle  (4)  of  the  second  arch  gives  rise  to  the  anthelix.  The 
ventral  tubercle  (6)  of  the  second  arch  produces  the  lobule.  It  should  be  noted 
that  in  the  third  month  the  dorsal  and  caudal  portions  of  the  helix  are  bent 
forward  and  conceal  the  anthelix. 

Anomalies. 

Malformations  of  the  nose  have  been  alluded  to  in  connection  with  hare  lip, 
cleft  palate,  etc.,  on  page  216,  and  are  also  discussed  in  the  chapter  on  tera- 
togenesis  (XIX) .  Malformations  affecting  the  eye  (cyclopia,  microphthalmia, 
etc.)  and  the  ear  (synotia,  etc.)  are  dealt  with  in  the  chapter  on  teratogenesis. 


602  TEXT-BOOK  OF  EMBRYOLOGY. 

PRACTICAL  SUGGESTIONS. 

THE  EYE. 

Embryos  of  the  chick,  pig  and  rabbit  furnish  excellent  and  easily  available  material  for 
the  study  of  the  development  of  the  eye.  They  should  be  fixed  in  Zenker'sor  Bouin's  fluid, 
embedded  in  paraffin,  sectioned  transversely  through  the  proper  levels,  stained  with  Weigert's 
hasmatoxylin  and  eosin,  and  mounted  in  xylol-damar. 

The  chick  embryo  of  twenty-four  to  twenty-eight  hours'  incubation  shows  the  three 
primary  brain  vesicles  and  the  optic  evaginations. 

At  thirty-six  hours'  incubation,  the  evagination  has  become  a  distinct  vesicle  connected 
with  the  brain  by  the  optic  stalk.  The  outer  wall  of  the  vesicle  lies  just  under  the  surface 
ectoderm,  which  is  here  thickened  to  form  the  lens  area. 

At  about  forty-eight  hours  the  lens  area  has  changed  to  a  distinct  invagination  and  the 
optic  vesicle  has  become  flattened. 

At  from  fifty-four  to  fifty-eight  hours  the  lens  invagination  has  become  much  larger,  and 
its  lips  have  begun  to  approximate.  The  optic  cup  is  at  this  stage  shallow  and  its  two  layers 
are  in  apposition  at  the  bottom  of  the  cup,  while  at  the  edges  of  the  cup  the  remains  of  the 
original  cavity  of  the  vesicle  are  still  visible. 

At  about  eighty-five  hours  a  distinct  lens  vesicle  has  been  formed,  which  is  completely 
separated  from  the  surface  ectoderm. 

At  about  ninety-five  hours  a  definite  lens  has  been  formed  with  long  nucleated  lens 
fibers  and  an  anterior  epithelium.  The  outer  layer  of  the  optic  cup  begins  to  show  pigment 
granules. 

Should  human  embryos  be  available,  the  following  data  may  be  of  service: 

At  what  has  been  estimated  as  about  four  weeks,  the  lens  is  formed  and  lies  in  the  mouth 
of  the  optic  cup.  It  is  separated  by  mesoderm  from  the  surface  ectoderm  (epithelium  of  the 
cornea).  The  optic  cup  shows  two  distinct  layers  the  outer  of  which  contains  pigment 
granules.  The  cavity  of  the  vitreous  shows,  as  does  also  a  layer  of  vascular  mesoderm 
surrounding  the  cup — the  anlage  of  the  chorioid. 

At  from  five  to  six  weeks  the  mesodermal  anlagen  of  the  substantia  propria  corneae  and 
of  the  tunica  vasculosa  lentis  can  be  seen.  The  vitreous  is  more  distinctly  formed  than  in 
the  preceding. 

At  from  seven  to  eight  weeks  the  lens  shows  distinct  lens  fibers  and  anterior  lens  epithe- 
lium. There  is  also  a  beginning  differentiation  between  the  chorioid  and  sclera. 

At  from  nine  to  ten  weeks  the  mesodermal  vessels  have  extended  into  the  vitreous,  both 
arteria  centralis  retinae  and  its  continuation  into  the  vitreous  as  the  hyaloid  artery  having 
developed.  Nerve  fibers  can  be  seen  in  the  periphery  of  the  optic  stalk.  These  can  be 
traced  to  the  nerve  cells  of  the  ganglion  cell  layer  of  the  retina. 

At  eleven  to  twelve  weeks  the  corneal  epithelium  shows  distinctly  and  the  substantia 
propria  corneae  has  become  differentiated  by  the  formation  of  the  anterior  chamber.  The 
eyelid  is  developed  to  the  edge  of  the  lens. 

At  from  thirteen  to  fifteen  weeks  the  eyelids  become  closed  with  the  formation  of  a  distinct 
conjunctival  sac.  The  chorioid  and  sclera  are  more  completely  differentiated.  There  are 
also  present  the  anlagen  of  the  lacrymal  glands,  of  the  Meibomian  glands  and  of  the  tarsus. 

At  sixteen  to  seventeen  weeks  the  ciliary  body  and  processes  begin  to  appear;  also  the 
iris,  the  differentiation  between  the  pars  optica  retinas  and  the  pars  ciliaris  and  pars  iridicae 
retinae,  the  membrana  pupillaris  and  the  lens  capsule.  The  anterior  chamber  has  also 
become  much  more  distinct. 


THE   ORGANS   OF  SPECIAL  SENSE.  603 

The  development  of  the  different  retinal  layers  can  be  studied  in  sections  treated  with  the 
above  technic,  but  for  the  study  of  the  development  of  the  various  nerve  elements  and  their 
relations  recourse  must  be  had  to  one  or  other  of  the  Golgi  methods  (see  "Practical  Sug- 
gestions," end  of  Chapter  XVII). 

THE  NOSE. 

The  nasal  pits  can  be  seen  as  depressions  at  the  sides  of  the  naso-frontal  processes  in 
human  embryos  of  6  to  8  mm.  (end  of  the  first  month),  and  in  other  mammalian  embryos  of 
corresponding  stages.  The  further  changes  in  the  outer  form  can  be  followed  in  succeeding 
stages. 

For  changes  in  the  interior,  sections  are  of  course  necessary.  A  very  instructive  stage  of 
the  development  of  the  nasal  septum,  nasal  chambers,  conchae,  and  palate  is  shown  in  pig 
embryos  of  25  by  30  mm.  (or  human  embryos  of  the  same  length;  see  Fig.  510).  Fix  the 
embryo  in  Zenker's  or  Bouin's  fluid,  cut  serial  sections  transverse  to  the  long  axes  of  the 
jaws,  stain  with  Weigert's  haematoxylin  and  eosin,  and  mount  in  xylol-damar.  Such  sections 
can  also  be  used  in  studying  the  dental  shelf  (see  Practical  Suggestions,  p.  359). 

THE  EAR. 

Owing  to  the  fact  that  the  ear  (especially  the  labyrinth)  is  so  complicated,  it  is  practically 
impossible  to  study  its  development  without  the  aid  of  reconstructions.  The  simple 
auditory  vesicle  can  be  seen,  however,  in  sections  of  pig  embryos  of  8  to  10  mm.,  lying  close 
to  the  side  of  the  neural  tube  in  the  hind-brain  region.  In  later  stages,  transverse  serial 
sections  should  be  cut  through  this  region  and  reconstructions  made  of  the  parts  of  the 
labyrinth.  The  same  technic  can  be  used  as  given  under  "The  Nose''  (see  above). 

References  for  Further  Study. 
THE  EYE. 

GALLENGA:  Entwickelung  des  Auges.  Encyklopddie  der  Augenheilkunde,  Lief.  6  and  7, 
1902. 

HOLDEN:  An  Outline  of  the  Embryology  of  the  Eye,  New  York,  1893. 

VON  KOLLIKER:  Die  Entwicklung  und  Bedeutung  des  Glaskorpers.  Zeitschr.  fur 
wissensch.  Zoolog.,  Bd.  LXVI,  1904. 

LANGE,  O.:  Einblicke  in  die  embryonale  Anatomie  und  Entwicklung  des  Menschen- 
auges.  1908. 

RABL,  C.:  Ueber  den  Bau  und  Entwickelung  der  Linse.  Zeitschr.  fur  wissensch.  Zool., 
Bd.  LXII  and  LXV,  1898;  LXVII,  1899. 

RAYMON  Y  CAJAL.:  Nouvelles  contributions  a  1'etude  histologique  de  la  retine.  Jour,  de 
VAnat.  et  de  la  PhysioL,  Vol.  XXXII,  1896. 

ROBIXSON.  A.:  On  the  Formation  and  Structure  of  the  Optic  Nerve  and  its  Relation  to 
the  Optic  Stalk.  Jour,  of  Anal,  and  Physiol.,  Vol.  XXX,  1896. 

VON  SPEE:   Recherches  sur  1'origine  du  corps  vitre.     Arch,  de  Biol.,  Vol.  XIX,  1902. 

THE  NOSE. 

BEARD,  J. :  Morphological  Studies.  The  Nose  and  Jacobson's  Organ.  Zool.  Jahrbuch, 
Bd.  Ill,  1889. 

DISSE,  J.:  Die  erste  Entwickelung  der  Riechnerven.     Anat.  Hefte,  Bd.  IX,  1897. 

His,  W.:  Beobachtungen  zur  Geschichte  der  Nasen-  und  Gaumenbildung  beim 
menschlichen  Embryo.  Abhandl.  d.  math.-phys.  Klasse  Konig.  Sachs.  Gesettsch.  d. 
Wissensch.,  1901. 


604  TEXT-BOOK  OF  EMBRYOLOGY. 

HOCHSTETTER,  F.:  Ueber  die  Bildung  der  primitiven  Choanen  beim  Menschen.  Ver- 
handl.  d.  anal.  Gesellsch.,  Bd.  VI,  1892. 

VON  MIHALKOWICZ,  V.:  Nasenhohle  und  Jacobsonsches  Organ.  Eine  morphologische 
Studie.  Anal.  Hefte,  Bd.  XI,  1898. 

PETER,  K.:  Die  Entwickelung  des  Geruchsorgans  und  Jacobson'schen  Organs  in  der 
Reihe  der  Wirbeltiere.  In  Hertwig's  Handbuch  d.  vergleich.  u.  experiment.  Entwickel- 
ungslehre  d.  Wirbeltiere,  Bd.  II,  Teil  II,  1901. 

THE  EAR. 

BAGINSKY,  B.:  Zur  Entwickelung  der  Gehorschnecke.  Arch.f.  mik.  Anat.,  Bd.  XXVIII, 
1886. 

BOETTCHER,  A.:  Ueber  Entwickelung  und  Bau  des  Gehorlabyrinths.  Verhandl.  d. 
Kais.Leop. -Carol.  Akad.,  Bd.  XXXV,  1869. 

BROMAN,  I.:  Die  Entwickelungsgeschichte  der  Gehorknochelchen  beim  Menschen. 
Anat.  Hefte,  Bd.  XI,  1898. 

FUCHS,  H.:  Bemerkungen  iiber  die  Herkunft  und  Entwickelung  der  Gehorknochelchen 
bei  Kaninchen-Embryonen.  Arch.f.  Anat.  u.  Phys.,  Anat.  Abth.,  Suppl.,  1905. 

HENSEN,  V.:    Zur  Morphologic  der  Schnecke.  Zeitschr.  f.  ivissensch.  Zool.,  Bd.  XIII,  1863 

His,  W.:  Zur  Entwickelung  des  Acusticofacialisgebiets  beim  Menschen.  Arch.f.  Anat. 
u.  Phys.,  Anat.  Abth.,  Suppl.,  1899. 

KRAUSE,  R.:  Entwickelungsgeschichte  des  Gehororgans.  In  Hertwig's  Handbuch  d. 
vergleich.  u.  experiment.  Entwickelungslehre  d.  Wirbeltiere,  Bd.  II,  Teil  II,  1902. 

STREETER,  G.  L.:  On  the  Development  of  the  Membranous  Labyrinth  and  the  Acoustic 
and  Facial  Nerves  in  the  Human  Embryo.  Am.  Jour,  of  Anat.,  Vol.  VI,  No.  2,  1907. 


CHAPTER  XIX. 

TERATOGENESIS. 

MALFORMATIONS  INVOLVING  MORE  THAN  ONE  INDIVIDUAL. 
Classification,  Description,  Origin. 

To  give  a  complete  list  of  the  numerous  malformations  in  man,  even  of 
those  which  affect  the  external  form  of  the  body,  is  obviously  beyond  the  scope 
of  this  book.  In  this  chapter  it  is  the  purpose  of  the  writers  merely  to  describe 
in  a  general  way  the  most  striking  malformations  and  discuss  briefly  the  causes 
underlying  the  origin  of  malformations.  For  further  details  concerning  the 
subject  the  student's  attention  is  directed  to  "References  for  Further  Study" 
(p.  627). 

The  classification  of  malformations  is  attended  by  great  difficulties.  This 
is  due  mainly  to  the  fact  that  their  complexities  are  not  wholly  understood.  It 
is  due  also  in  a  measure  to  the  fact  that,  apart  from  certain  malformations 
which  always  occur  in  like  manner  in  different  individuals,  there  are  so  many 
irregularities  and  deviations  from  any  type  that  might  arbitrarily  be  chosen. 
The  classification  made  by  St.  Hilaire  three-quarters  of  a  century  ago, 
although  apparently  complete,  showed  many  incongruities  as  teratology 
became  more  firmly  established  upon  an  embryological  basis.  Later 
Bischoff  formulated  a  division  based  upon  the  embryological  significance 
of  malformations.  This  in  turn  was  elaborated  by  Forster,  and  Forster's 
scheme  has  been  adopted  by  Marchand  and  others.  As  knowledge  concern- 
ing teratogenesis  is  added  to,  it  may  be  that  further  changes  in  classification  will 
be  necessary,  especially  in  view  of  the  fact  that  much  light  is  being  thrown  by 
experimental  methods  upon  the  origin  of  malformations. 

Marchand's  scheme  of  duplicate  monsters  is  given  here  as  a  convenient  one 
for  a  comprehensive  view  of  anomalous  conditions  affecting  two  individuals. 
I.  Both  bodies  derived  from  anlagen  which  developed  from  one  ovum 
and    which    were    originally  similar   and    symmetrical:    Symmetrical 
•  duplicity. 

A.  Both  bodies  originally  complete :     Complete  duplicity. 

i.  The  two  bodies  remain  separate;  union  confined  to  chorion: 
Twins;  free  duplicities. 

a.  Both  bodies  formed  alike,  each  capable  of  living:    Equal 
monochorionic  twins. 
605 


(306  TEXT-BOOK  OF  EMBRYOLOGY. 

b.  One  body  normal,  the  other  abnormal  or  much  mal- 
formed:    Unequal  monochorionic  twins. 

2.  The  two  bodies  united;  formed  alike  (equal),  or  one  remains 
more  or  less  rudimentary  (unequal) :  Twins  joined  together; 
duplicate  monsters. 

a.  Union  confined  to  lower  end  of  body:     Double  monsters 
with  posterior  union;  anterior  duplicity. 

b.  Union  confined  to  middle  of  body,  or  extending  from 
middle  forward:     Double  monsters  with  middle  union. 

c.  Union  limited  to  upper  end  of  body,  or  extending  from 
upper  end  downward:     Double  monsters  with  anterior 
union;  posterior  duplicity. 

B.  Duplicity  does  not  affect  entire  anlage,  but  only  a  part :   Incomplete 
duplicity. 

1.  Two  incomplete  anlagen  (or  primitive  streaks)  pass  over  into 
a  single  anlage:    Posterior  incomplete  duplicity. 

2.  An  originally  single  anlage  forms  by  dichotomous  growth  two 
separate  upper  (anterior)  ends:  Anterior  incomplete  duplicity. 

In  addition:     Triplicity,  quadruplicity,  etc.,  (multiplicity). 
II.  Both   bodies   derived   from   two   originally  dissimilar,   asymmetrical 
anlagen,  of  which  one,  always  rudimentary,  becomes  more  or  less  en- 
closed and  nourished  by  the  other:  True  parasitic  duplicity;  asym- 
metrical duplicity. 

In  addition:     Teratoid  tumors. 

SYMMETRICAL  DUPLICITY. 

As  seen  from  the  foregoing  scheme,  there  are  included  under  this  head 
double  forms  in  which  both  embryos  develop  within  a  single  chorion  (mono- 
chorionic twins),  and  in  which  the  bodies  may  be  distinct  and  separate 
(complete  duplicity)  or  may  be  united  (incomplete  duplicity).  In  complete 
duplicity  each  embryo  usually  possesses  its  own  amnion  and  umbilical  cord, 
but  both  are  attached  to  the  same  placenta.  In  such  cases  the  conditions  of 
nutrition  and  rate  of  growth  may  be  so  similar  in  the  two  individuals  that  their 
development  is  equal  (equal  monochorionic  twins).  They  may  grow  to 
maturity,  and  they  always  bear  a  remarkable  resemblance  to  each  other  in 
physical  features  and  in  mental  characteristics  and  are  always  of  the  same 
sex.  More  commonly,  however,  the  development  of  separate  monochorionic 
twins  is  unequal,  caused  probably  by  dissimilar  conditions  of  nutrition.  In 
some  instances  the  less  favored  individual  is  but  slightly  affected,  so  that  it 
may  be  born  and  be  able  to  maintain  an  independent  existence.  On  the  other 


TERATOGENESIS.  607 

hand,  the  nutrition  of  one  embryo  may  be  so  seriously  impaired  that  it  dies. 
When  death  occurs  during  the  earlier  months  of  pregnancy  the  dead  embryo 
is  subjected  to  pressure  by  the  living  one  and  is  sometimes  distorted  and 
flattened  into  a  thin  mass  known  as  a  foetus  papyraceus. 

Equal  growth  of  monochorionic  twins  implies  an  almost  perfect  nutritive 
balance,  since  both  embryos  derive  their  nourishment  from  the  same  placenta. 
Any  condition  that  disturbs  the  nutritive  balance  tends  to  affect  adversely  the 
less  favored  embryo,  so  that  development  does  not  proceed  equally  (unequal 
monochorionic  twins).  One  of  the  first  consequences  of  such  a  disturbance 
may  be  an  impaired  or  arrested  development  of  the  heart,  in  which  case  the 
weaker  embryo  may  become  an  acardiac  monster. 

This  condition  does  not  necessarily  imply  the  absence  of  the  heart  in  the 
affected  twin;  for  it  may  possess  a  functionating  heart,  or  it  may  become  an 
amorphous  mass  of  tissue  which  derives  its  total  blood  supply  through  the 
action  of  the  heart  of  the  stronger  twin,  or  there  may  be  any  form  between  the 
two  extremes.  In  any  case  the  •  acardiac  monster — acardiacus — receives  its 
blood  wholly  or  in  part  through  the  agency  of  the  stronger  heart. 

Acardia  is  always  accompanied  by  a  so-called  "reversal  of  the  circulation;" 
and  there  are  three  periods  at  which  it  may  originate,  (i)  It  may  originate 
before  the  heart  develops.  As  is  well  known,  the  heart  appears  independently 
of  the  area  vasculosa  and  joins  the  vessels  secondarily  (p.  222).  If,  for  any 
reason,  the  heart  of  one  of  the  embryos  fails  to  develop,  anastomoses  may 
occur  between  the  vascular  anlagen  of  the  two  vascular  areas  and  consequently 
the  normal  embryo  assumes  the  duty  of  nourishing  the  other.  The  latter  be- 
comes an  acardiac  monster.  (2)  It  may  originate  after  the  heart  has  begun  to 
develop,  but  before  the  placental  circulation  is  established.  If,  for  any  reason, 
the  heart  of  one  embryo  should  cease  to  develop  further,  there  would  probably 
be  sufficient  anastomoses  between  the  vitelline  vessels  of  the  two  embryos  to 
enable  the  affected  embryo  to  live  and  become  an  acardiac  parasite.  In  this 
case  no  placental  circulation  would  develop  in  the  parasite.  (3)  Acardia  may 
originate  after  the  establishment  of  the  placental  circulation.  Since  there  is 
but  one  chorion  or  placenta  for  both  embryos  there  is  naturally  a  communica- 
tion between  the  two  circulations  in  the  chorionic  villi.  There  are  also  likely 
to  be  anastomoses  between  the  umbilical  arteries  and  veins.  If,  for  any  reason, 
the  heart  action  of  one  of  the  embryos  should  become  impaired,  there  would  be 
an  influx  of  blood  into  the  vessels  of  that  embryo  owing  to  diminished  pressure. 
Thus  the  blood  from  the  stronger  heart  would  be  pumped  into  the  affected 
embryo  as  wTell  as  into  the  placenta.  This  blood,  being  impure,  fails  to  nourish 
the  weaker  embryo  properly  and  the  result  is  atrophy  or  degeneration. 

Upon  the  basis  of  other  malformations  that  naturally  accompany  impaired 
development  of  the  heart,  acardiac  monsters  are  divided  into  four  classes. 
39 


608  TEXT-BOOK  OF  EMBRYOLOGY. 

i.  Acardiacicompleti. — The  general  development  of  the  acardiacus  depends  upon 
the  sufficiency  of  the  blood  supply  which  it  receives.  If  there  is  a  well  developed 
anastomosis  between  the  two  placental  circulations  the  weaker  embryo  may 
receive  a  moderately  good  blood  supply  and  develop  into  a  fairly  normal  foetus. 
A  well  formed  trunk  and  head  may.be  present  and  the  extremities  may  be 
represented  in  part  or  in  full.  2.  Acardiaci  acormi. — These  may  possess  only  a 
head,  or  they  may  possess  a  head  and  traces  of  a  trunk  and  extremities. 
Their  evolution  depends  upon  unusual  combinations  of  anastomoses  in  their 
venous  channels.  3.  Acardiaci  acephali. — No  head  is  present.  The  lower 
part  of  the  trunk  is  present,  and  sometimes  other  parts  of  the  trunk.  The  ex- 
tremities may  be  complete,  incomplete  or  absent.  These  forms  are  also  due 
to  peculiar  combinations  of  vascular  anastomoses.  4.  Acardiaci  amor  phi. — As 
the  name  indicates,  there  is  no  typical  form  for  the  affected  embryo.  It  bears  no 
resemblance  to  a  normal  embryo,  but  is  merely  an  irregular  mass  of  tissue. 

In  symmetrical  duplicity,  instead  of  the  two  embryos  in  one  chorion  being 
distinct  and  separate  individuals,  they  may  be  joined  together  to  a  greater  or 
lesser  extent.  The  two  individuals  may  develop  to  practically  the  same 
degree  (equal  united  twins,)  or  one  may  remain  more  or  less  rudimentary 
(unequal  united  twins.)  As  may  be  seen  by  reference  to  the  scheme  on  page  605, 
there  are  three  modes  of  union — posterior,  middle  and  anterior. 

Posterior  Union. — This  may  be  either  dorsal  or  ventral.  In  dorsal  posterior 
union  the  two  bodies  are  joined  together  in  the  pelvic  region,  with  the  dorsal 
surfaces  of  the  twins  directed  toward  each  other.  The  umbilicus  is  double  and 
the  two  umbilical  cords  converge  toward  a  common  placenta — pygopagus. 
The  general  anatomical  features  are  as  follows.  There  is  a  single  coccyx 
and  a  single  sacrum;  pelvic  bones  and  symphyses  are  present  in  normal 
number;  near  the  ends  of  the  large  intestines  the  two  digestive  tubes  unite  to 
form  a  common  lumen,  and  the  two  recta  open  through  a  common  anus  between 
the  more  dorsally  situated  pair  of  extremities;  the  two  spinal  cords  unite  near 
their  lower  ends  to  form  a  single  conus  and  filum  terminale;  the  urogenital 
tracts  are  united  only  to  a  slight  degree.  This  form  of  monster  is  of  interest 
because  it  is  able  to  live  for  years;  indeed  a  number  of  them  have  lived  to 
maturity. 

In  case  of  ventral  posterior  union  the  attachment  may  be  confined  to  the 
pelvic  region  or  may  involve  the  entire  trunk.  In  the  former  instance — 
ischiopagus — the  right  pubic  bone  of  one  pelvis  fuses  with  the  left  pubic  bone 
of  the  other  pelvis,  the  ventral  surfaces  of  the  two  sacra  facing  each  other. 
The  axes  of  the  bodies  may  be  in  line,  or  they  may  form  an  angle.  The  con- 
tinuous ventral  surfaces  of  the  two  bodies  contain  a  single  umbilicus.  The 
organs  in  the  pelvic  region  may  be  single  or  double.  The  lower  extremities 
may  be  fully  developed,  or  there  may  be  only  three,  or  rarely  two.  Sometimes 


TERATOGENESIS.  609 

one  of  the  twins  is  rudimentary,  the  thorax  and  head  being  absent,  but  the 
extremities  present  in  part  (ischiopagus  parasiticus) .  Ischiopagi  seldom 
survive  owing  to  atresia  of  the  anus. 

In   case   the   attachment   extends  along  the  entire  trunk  of  each  twin • 

ischiothoracopagus — the  two  sacra  are  usually  fused  to  form  a  single  sacrum. 
The  thoraces  of  the  twins  are  joined  by  means  of  a  common  sternum.  The 
upper  extremities  may  all  be  present  (tetrabrachius),  or  there  may  be  three 
(tribrachius),  or  only  two  (dibrachius)  and  a  very  rudimentary  third.  The 
lower  extremities  are  subject  to  the  same  variations  as  the  upper.  The  ex- 
ternal genitalia  and  anus  are  single.  The  alimentary  tube  is  double  as  far  as 
the  lower  end.  The  thoracic  viscera  are  partly  double.  Monsters  of  this 
type  may  live  for  years. 

Middle  Union. — In  the  case  of  middle  union  a  ventral  or  ventro-lateral 
attachment  extends  from  the  umbilicus  for  a  variable  distance  toward  the  head. 
In  most  cases  the  umbilicus  itself  is  single.  The  union  may  occur  in  the 
region  of  the  xiphoid  process — xiphopagus — or  it  may  involve  the  entire  region 
of  the  sternum — sternopagus  or  thoracopagus.  In  the  case  of  xiphopagus, 
a  bridge  joining  the  twins  extends  from  the  common  umbilicus  to  the 
xiphoid  processes.  The  latter  are  usually  united  across  the  bridge.  The 
thoracic  cavities  are  separate.  The  two  livers  may  be  connected  by  a  bridge  of 
hepatic  tissue,  in  which  case  the  two  peritoneal  cavities  are  in  communication, 
or  the  livers  may  remain  separate,  in  which  case  the  peritoneal  cavities  do  not 
communicate.  The  two  alimentary  tubes  may  or  may  not  communicate  in  the 
region  of  the  stomach.  Xiphopagi  may  live  for  many  years,  as  instanced  by 
the  "Siamese  Twins." 

In  the  case  of  sternopagus  the  union  extends  upward  from  the  common  um- 
bilicus, so  that  the  two  sterna  are  fused  into  a  single  bone.  There  is  a  com- 
mon thoracic  cavity,  separated  from  the  abdominal  cavity  by  a  single  diaphragm. 
One  or  two  hearts  may  be  present.  The  middle  portions  of  the  two  alimentary 
tubes  form  a  single  tract.  The  two  livers  are  fused  into  a  common  mass.  The 
genitalia  are  distinct  and  separate.  The  extremities  may  be  normal,  or  in  case 
of  a  ventro-lateral  union,  the  approximated  upper  extremities  may  be  fused. 
Such  monsters  are  usually  born  dead;  if  born  alive,  they  survive  but  a  short 
time  owing  to  defective  development  of  the  heart. 

As  other  varieties  of  thoracopagus  the  following  may  be  mentioned :  Thora- 
copagus parasiticus,  in  which  one  twin  is  much  arrested  in  development,  a  head 
and  heart  being  present,  and  attached  to  the  thoracic  region  of  the  stronger 
twin.  Gastrothoracopagus  dipygus  (dipygus  parasiticus),  in  which  extremities 
and  trunk  are  present  at  least  in  part  and  are  attached  to  the  lower  part  of  the 
thorax  or  to  the  epigastrium  of  the  other  twin.  The  head  is  not  present.  Such 
twins  may  live  for  years,  as  instanced  by  Laloo.  Cephalothoracopagus  diproso- 


610  TEXT-BOOK  OF  EMBRYOLOGY. 

pus,  in  which  the  attachment  may  extend  into  the  neck  and  head  region,  so 
that  there  is  a  union  from  the  head  to  the  umbilicus.  This  type  is  distinguished 
from  the  anterior  union  in  that  the  head  portions  of  the  twins  are  united 
laterally,  so  that  both  more  or  less  completely  developed  faces  are  turned 
toward  the  common  ventral  side,  while  the  bodies  have  their  ventral  sides 
directed  toward  each  other. 

Anterior  Union. — In  this  type  of  union  the  attachment  may  be  dorsal  and 
confined  to  the  head  (dorsal  anterior  union),  or  ventral  and  reaching  as  far  as 
the  umbilicus  (ventral  anterior  union). 

In  dorsal  union  the  heads  of  the  twins  are  joined  at  the  crowns,  so  that 
the  two  bodies  lie  in  a  straight  line,  or  form  an  angle  with  each  other.  Such 
a  monstrosity  is  known  as  craniopagus  (cephalopagus).  The  attachment 
usually  involves  the  cranial  vault,  the  two  brains  remaining  separated  by 
their  membranes  within  a  common  cranial  cavity.  Such  monsters  are  rare 
and  survive  but  a  short  time.  A  very  rare  variety  of  craniopagus  is  the 
form  known  as  craniopagus  parasiticus,  in  which  one  twin  is  reduced  to  a 
rudimentary  structure  and  is  parasitic  upon  the  other.  In  all  the  above  cases 
the  term  autosite  is  applied  to  the  better  developed  twin. 

In  ventral  and  ventro-lateral  union  the  attachment  involves  the  head, 
neck  and  thorax — syncephalus,  cephalothoracopagus  janiceps.  The  twins  pass 
through  their  development  in  common,  each  individual  contributing  its 
quota  of  structure  to  the  composite  monster.  The  sternum  is  single,  the  oeso- 
phagus single,  the  larynx  and  trachea  double  or  single,  the  stomach  single,  the 
intestine  double.  The  two  hearts  may  be  united,  but  more  commonly  are 
separated,  one  being  situated  ventrally,  the  other  dorsally.  Two  faces  are 
formed,  one  belonging  to  each  embryo.  The  faces  may  be  alike  or  nearly  so 
(Janus  symmetros),  or  one  may  be  misplaced  or  unequally  developed  (Janus 
asymmetros),  which  often  results  in  cyclopia,  synotia,  or  obliteration  of  the 
opening  of  the  mouth. 

In  some  cases  the  greater  part  of  the  body  is  single  and  only  a  part  is  double 
(incomplete  duplicity).  The  malformation  may  affect  only  the  upper  end  or 
head  (superior  incomplete  duplicity),  or  only  the  lower  end  (inferior  incomplete 
duplicity).  In  the  former  case  the  skull  is  single,  with  possible  traces  of  a 
double  formation — diprosopus.  There  are  two  faces  with  varying  degrees  of 
fusion  between  them;  all  four  eyes  may  be  present,  or  the  two  approximated 
eyes  may  be  fused  or  they  may  be  wanting  (diprosopus  tetroph-,  trioph-, 
diophthalmus).  The  two  mouths  may  be  fused  (diprosopus  monostomus), 
and  with  a  greater  degree  of  fusion  between  the  faces  the  two  approximated 
ears  may  also  be  fused  or  be  entirely  lacking.  In  dicephalus  the  head  is 
double,  and  sometimes  the  upper  end  of  the  vertebral  column. 

Inferior  incomplete  duplicity  is  rare.     To  this  category  of  duplicate  monsters 


TERATOGENESIS.  611 

probably  belong  certain  cases  of  partial  duplicity  in  the  pelvic  region,  with 
sometimes  an  extra  set  of  genitalia.  Possibly  also  a  few  cases  of  a  third  lower 
extremity  would  come  under  this  head. 

Multiplicity. — Monochorionic  triplets  are  rare,  only  a  few  cases  being 
recorded.  Two  cases  of  monochorionic  quadruplets  are  on  record,  and 
one  case  of  quintuplets.  Incomplete  multiplicities  are  extremely  rare.  One 
case  of  incomplete  triplicity  has  been  described — tricephalus.  Two  verte- 
bral columns  were  present  in  this  monster,  bearing  one  and  two  heads  re- 
spectively. Two  thoracic  cavities,  each  enclosing  a  heart,  were  separated  by 
a  thin  septum.  The  abdominal  viscera  were  single.  The  lower  half  of  the 
body  and  the  lower  extremities  were  normal,  as  were  also  the  genital  organs, 
which  were  male. 

ORIGIN  OP  SYMMETRICAL  DUPLICITY. 

The  origin  of  duplicities  has  alwrays  been  most  difficult  to  explain,  and 
the  many  solutions  suggested  have  been  replete  with  conjecture.  The  diffi- 
culty has  been  caused  by  the  lack  of  direct  observation  upon  formative  stages 
either  in  the  lower  or  higher  animals.  Within  recent  years,  however,  experi- 
mental work  upon  the  lower  forms  has  begun  to  throw  some  light  upon  this 
obscure  problem.  Among  the  theories  which  have  been  formulated  are  two 
that  stand  out  most  clearly — the  fusion  theory  (Marchand,  Ziegler)  and  the 
fission  theory  (Ahlfeld  and  others). 

According  to  the  fusion  theory,  there /are  present  two  originally  distinct 
anlagen  within  a  single  ovum.  These  two  anlagen  may  develop  separately  and 
independently  and  produce  twins.  They  may  come  in  contact  during  develop- 
ment and  fuse  to  a  greater  or  lesser  degree,  thus  producing  some  kind  of  dupli- 
cate monster.  If  fusion  does  occur  it  occurs  between  similar  parts  of  the  two 
anlagen;  in  other  words,  like  tissues  and  organs  fuse — liver  with  liver,  muscle 
with  muscle,  bone  with  bone,  and  so  on.  Such  unions,  however,  probably 
occur  only  in  very  early  stages  of  development,  for  when  tissues  are  once  formed, 
union  is  effected  with  much  greater  difficulty.  Consequently  fusions  between 
two  anlagen,  leading  to  double  monsters,  probably  take  place  at  a  very  early 
period  of  intrauterine  life. 

According  to  the  fission  theory,  duplicity  is  the  result  of  the  division  of  a 
single  anlage  in  the  earliest  stages  of  development,  before  the  formation  of  the 
primitive  streak.  The  cleavage  is  produced  by  mechanical  resistance  of  the 
zona  pellucida.  Since  the  greatest  mass  of  growing  material  is  in  the  head 
region,  the  resistance  is  greatest  there,  and  hence  it  is  argued  that  duplicities 
would  be  most  common  in  the  head  region,  which  accords  with  the  facts.  A 
modification  of  the  fission  theory  to  explain  duplicities  which  affect  a  relatively 
small  area  has  been  suggested.  Incomplete  anterior  duplicity,  for  example,  is 


612  TEXT-BOOK  OF  EMBRYOLOGY. 

not  the  result  of  fission  but  of  bifurcation  which  accompanies  the  development 
of  the  head  end  of  the  embryo  along  divergent  axes.  The  difference  between 
fission  and  bifurcation  is  that  the  former  is  the  passive  result  of  active 
mechanical  forces,  while  the  latter  is  a  part  of  active  formative  processes. 

Experiments  on  eggs  of  lower  animals  point  to  the  conclusion  that  each  of 
the  two  blastomeres  resulting  from  the  first  cleavage  contains  the  material 
necessary  to  produce  an  entire  body.  In  order  to  cause  a  blastomere  to  pro- 
duce a  whole  body,  however,  it  is  necessary  to  subject  it  to  unnatural  conditions. 
For  example,  if  one  of  the  two  primary  blastomeres  of  the  frog  is  killed  and  the 
other  left  to  grow  in  its  natural  position  it  will  produce  a  half-embryo;  but  if  the 
remaining  blastomere  is  inverted  it  will  produce  a  whole  embryo  (Morgan). 
On  the  other  hand,  in  view  of  certain  experiments  on  the  eggs  of  Amphioxus, 
it  has  been  asserted  that  duplicity  is  associated  with  double  gastrulation; 
when  these  eggs  were  shaken  during  the  first  cleavage,  some  developed  into 
double  gastrulae  (Wilson,  Hertwig).  For  a  further  discussion  of  these  causes, 
see  page  624. 

ASYMMETRICAL  DUPLICITY. 

In  this  type  of  malformation  the  two  anlagen  from  which  the  monster  is 
derived  are  primarily  dissimilar  and  unequal.  One  anlage  usually  remains  in 
a  rudimentary  condition,  bears  little  or  no  resemblance  to  a  foetus,  and 
becomes  a  parasite  upon  or  within  the  body  derived  from  the  other  anlage 
(parasite,  foetal  inclusion,  foetus  in  fcetu).  Sometimes,  however,  the  dependent 
embryo  may  develop  quite  complete  parts,  such  as  extremities,  but  always 
remains  attached  to  the  stronger  embryo,  from  which  it  derives  its  nourishment 
(implantation).  Parasitic  inclusions  and  implantations  may  be  attached  to 
the  autosite  in  the  region  of  the  head,  neck,  thorax,  abdomen,  etc. 

Parasitic  duplicities  in  the  head  region  may  take  the  form  of  masses  pro- 
truding from  the  orbital  region — prosopopagus  parasiticus  or  much  more  com- 
monly from  the  mouth — epignathus,  sphenopagus.  In  the  latter  case  the  tumor 
is  enveloped  by  skin  containing  hair  follicles  an*d  sweat  glands,  and  usually 
consists  of  cysts  and  intervening  embryonic  tissue.  It  sometimes  contains  teeth, 
cartilage,  bone,  fat  and  nerve  tissue,  even  traces  of  an  intestinal  canal  and 
of  liver  tissue.  One  epignathus  has  been  described  as  having  an  imperfect 
set  of  female  genitalia  which  lay  between  two  rudimentary  lower  extremities. 

Occasionally  irregular  tumors  are  found  in  the  region  of  the  pituitary  body 
(encranius),  which  contain  rudiments  of  various  tissues  and  organs.  In  such 
cases  the  parasitic  anlage  has  possibly  been  included  during  the  imagination 
which  forms  the  oral  part  of  the  pituitary  body.  Tumors  consisting  of  various 
tissues,  such  as  lymphatic,  adipose,  muscle,  etc.,  are  also  found  in  the  brain 


TERATOGENESIS.  613 

ventricles.  They  possibly  represent  parasitic  anlagen  which  have  become  en- 
closed within  the  brain  vesicles  as  the  neural  groove  closed  in  dorsally. 

Certain  foetal  inclusions  attached  to  the  region  formed  by  the  branchial 
arches  are  spoken  of  as  cervical  parasites.  These  are  usually  cystic  tu- 
mors, covered  with  skin  and  containing  teeth,  bone  and  parts  of  a  head  and 
extremities. 

Closely  associated  with  the  cervical  parasites  is  a  group  of  tumors  found 
within  the  anterior  mediastinum  in  the  region  of  the  thymus  gland,  and  known 
as  thoracic  parasites.  It  must  be  borne  in  mind,  how;ever,  that  some  of  the 
tumors  found  in  the  cervical  and  thoracic  regions  are  not  true  parasitic  in- 
clusions, but  are  dermoid  cysts  (resembling  the  parasites)  derived  from  the 
ectoderm.  True  parasitism  implies  origin  from  all  three  germ  layers.  From 
a  structural  standpoint  it  is  sometimes  very  difficult,  even  impossible,  to  distin- 
guish between  true  parasitic  inclusions  and  dermoid  cysts  that  are  derived  from 
ectoderm. 

Very  rarely  in  the  human  subject  some  parasitic  structure  is  attached  to  the 
back.  One  case  of  a  supernumerary  penis  in  the  lumbar  region  has  been  de- 
scribed; another  case  is  on  record  of  an  almost  complete  set  of  female  genitalia 
on  the  back  of  a  male.  Such  malformations  can  be  explained  only  by  assum- 
ing the  partial  development  of  another  embryonic  anlage. 

Sacral  parasites  are  the  most  frequent  of  the  true  parastic  growths.  These 
are  cystic  tumors  which  are  attached  to  and  hang  from  the  sacrum  or  the 
coccyx.  The  tumors  are  covered  with  skin  which  blends  with  the  skin  of  the 
autosite.  In  the  existence  of  such  elements  as  fat,  bone,  muscle,  and  nerves, 
and  the  rudiments  of  intestines  and  extremities  is  found  the  evidence  of  their 
foetal  origin. 

Foetal  inclusions  in  the  abdominal  region  are  not  frequent.  One  very  rare 
intraparietal  (or  subcutaneous)  inclusion,  in  a  child  two  and  one-half  years 
old,  proved  to  be  a  cystic  tumor  which  contained  a  fairly  well  formed  foetus 
with  defective  head  and  extremities.  Engastric  (intraabdominal)  parasites 
are  usually  found  in  the  region  of  the  lesser  peritoneal  sac,  at  the  root  of  the 
transverse  mesocolon.  These  tumors  are  usually  enclosed  within  a  sac  of 
mesenteric  or  peritoneal  tissue.  There  may  be  well  marked  fcetal  structures, 
such  as  head,  trunk,  extremities,  etc.,  or  only  traces  of  rudimentary  organs. 
The  presence  of  an  intraabdominal  parasite  does  not  necessarily  cause  the 
death  of  the  autosite  immediately  after  birth;  for  one  case  in  particular  is  on 
record  in  which  the  autosite  (a  boy)  lived  to  be  fifteen  -ears  old  with  a  parasite 
that  was  capable  of  independent  movement. 

Parasitic  Structures  in  the  Sexual  Glands. — The  type  of  tumor  referred  to 
here  forms  a  group  that  is  of  especial  interest  owing  to  their  relative  frequency 
of  occurrence  and  to  their  peculiar  mode  of  production.  In  connection  with 


G14  TEXT-BOOK  OF  EMBRYOLOGY. 

the  ovary  dermoid  cysts  and  other  solid  masses  occur.  The  cysts  consist  of  a 
sac  enclosing  hair  and  adipose  tissue;  not  infrequently  teeth  are  also  present,  as 
well  as  sebaceous  and  sweat  glands.  Sometimes  there  are  also  bone,  cartilage, 
muscle,  and  nerve  tissue  and  traces  of  the  digestive  and  respiratory  systems  and 
of  thyreoid  gland;  more  rarely  traces  of  mammary  glands,  finger  nails  and 
retinal  pigment  are  present.  In  the  rarer  solid  tumors  that  develop  in  rela- 
tion to  the  ovary  all  three  germ  layers  are  represented,  but  their  derivatives 
are  more  rudimentary  and  not  so  regularly  arranged  as  in  the  cysts. 

Parasitic  growths  in  the  testis  are  much  less  frequent  than  in  the  ovary. 
The  cysts  are  rarer  than  the  solid  masses.  These  are  probably  homologous 
with  the  parasites  of  the  ovary. 

ORIGIN  OF  ASYMMETRICAL  (PARASITIC)  DUPLICITY. 

Parasitic  duplicity  implies  primary  inequality  of  the  embryonic  anlagen;  in 
other  words,  the  anlage  of  the  parasite  is  inferior,  so  to  speak,  to  the  anlage  of 
the  host.  During  development  the  inequality  or  asymmetry  persists  or  be- 
comes more  conspicuous  until  the  parasite  is  more  or  less  enclosed  within  the 
autosite.  As  the  autosite  develops  in  a  manner  at  least  simulating  the  normal, 
the  parasite  remains  in  a  more  or  less  rudimentary  condition,  with  perhaps  only 
a  few  tissues  which  show  any  differentiation.  In  some  cases  the  parasite 
becomes  enclosed  partially  or  completely  within  the  autosite  (epignathus),  in 
other  cases  the  parasitic  growth  apparently  occurs  primarily  within  the  autosite 
(ovarian  cysts). 

The  manner  in  which  the  rudimentary  anlage  becomes  surrounded  by  the 
more  nearly  perfect  anlage  is,  of  course,  not  known  through  direct  observation. 
But  it  seems  reasonable  to  assume  that  such  enveloping  occurs  in  connection 
with  or  as  a  part  of  the  normal  processes  of  folding  by  which  the  external  form 
of  the  body  is  established.  This  folding  occurs  at  the  cephalic  and  caudal  poles 
of  the  embryonic  disk  and  also  along  its  entire  length.  In  addition  there  is 
also  the  folding  in  of  the  neural  groove  along  the  dorsum  of  the  embryo,  and 
the  invagination  of  the  branchial  grooves.  One  can  readily  imagine  the  para- 
sitic anlage  as  attached  to  some  one  of  the  areas  that  are  folded  in,  so  that 
it  is  carried  wholly  or  partially  into  the  interior  of  the  stronger  embryonic 
anlage  and  becomes  surrounded  by  the  tissues  of  the  autosite  to  produce  a 
true  foetal  inclusion. 

There  seems  to  be  little  doubt  as  to  the  existence  of  a  second,  more  or  less 
rudimentary  anlage  which  becomes  the  parasite;  in  other  words,  there  is  almost 
certainly  a  duplicity  to  begin  with,  although  it  may  be  an  asymmetrical  one. 
It  is  also  plausible  to  assume  that  for  a  time  the  weaker  anlage  develops  in- 
dependently of  the  stronger,  but  that  later  it  is  dependent  upon  the  stronger 


TERATOGENESIS.  615 

for  its  nutrition.  The  problem,  however,  is  to  explain  the  origin  of  the  rudi- 
mentary anlage  which  produces  the  parasite.  In  view  of  the  facts  concerning  the 
early  stages  of  development — the  facts  concerning  maturation,  fertilization  and 
segmentation  of  the  ovum,  and  the  formation  of  the  germ  layers — there  are  two 
possible  and  plausible  modes  of  origin  of  the  rudimentary  anlage.  (i)  The 
anlage  of  the  parasite  may  be  the  result  of  the  imperfect  development  of  a 
fertilized  polar  body.  (2)  The  anlage  of  the  parasite  may  be  a  special  or  an 
isolated  group  of  segmentation  cells. 

1.  It  is  generally  agreed  that  the  polar  bodies  are  abortive  or  rudimentary 
ova  extruded  during  the  processes  of  maturation  of  the  female  sex  cell;  and  that 
these  rudimentary  ova  probably  contain  the  same  morphological  constituents 
as  the  mature  ovum  itself.     It  is  also  known  that  in  a  few  of  the  lower  forms 
the  polar  bodies  arc  capable  of  being  fertilized  and  undergoing  a  considerable 
degree  of  development,  and  that  in  some  of  the  higher  forms  (rabbit,  dog)  the 
spermatozoa  may  exist  for  some  time  inside  the  zona  pellucida  in  the  vicinity 
of  the  polar  bodies.     In  view  of  these  facts  it  does  not  seem  impossible  that  in 
a  few  exceptional  cases  in  Mammals  the  polar  bodies  may  become  fertilized 
and  produce  rudimentary  anlagen  capable  of  giving  rise  to  parasites.     Such 
an  anlage  would  naturally  lie  in  close  proximity  to  the  larger  normal  anlage 
and    might   readily  become  attached  to  or  finally  enclosed  within  it.     As  a 
more  remote  possibility,  the  polar  body  might  become  enclosed  between  the 
blastomeres  and   thus  finally  produce  the  parasitic  anlage  within  the  meso- 
dermal  tissue  where  it  might  become  an  inclusion  in  some  internal  organ, 
such  as  the  genital  gland.     A  polar  body  has  been  found  between  the  blasto- 
meres (rabbit).     (Bischoff,  Assheton,  Bonnet.) 

2.  The  view  that  the  parasite  may  arise  as  the  result  of  the  development  of  a 
special  or  an  isolated  group  of  segmentation  cells  has  more  advocates  than  the 
view  given  in  the  preceding  paragraph.     One  of  the  most  interesting  phases  of 
this  theory  is  the  view  that  tumors  of  the  sexual  glands,  as  well  as  those  of  other 
regions,  are  the  products  of  development  of  the  germ  cells  as  distinguished  from 
the  somatic  cells.     In  the  skate  it  has  been  demonstrated  that  certain  cells  are 
set  apart  at  a  very  early  period  of  development  (during  segmentation),  which 
are  destined  to  give  rise  to  the  sex  cells  of  the  embryo,  and  which  take  no 
part  in  its  general  development.     Normally  these  special  cells  pursue  a  course 
of  development  and  differentiation  which  leads  to  the  formation  of  the  mature 
sexual  elements  (ova  or  spermatozoa)  of  the  individual,  but  do  not  participate 
in  its  general  development.     From  this  one  may  conclude  that  the  primitive 
germ  cell,  the  one  set  apart  for  the  production  of  the  mature  sex  cells,  is,  so 
to  speak,  a  sister  to  the  embryo  and  is  not  a  derivative  of  the  embryo.     It 
seems  not  impossible  that  some  aberrant  members  of  this  group  of  germ  cells, 
without  undergoing  the  changes  incident  to  maturation,  might  pursue  a  course 


616  TEXT-BOOK  OF  EMBRYOLOGY. 

of  development  of  their  own  accord  and  give  rise  to  a  rudimentary  twin — the 
fetal  inclusion  or  parasite.  In  this  case  one  must  regard  the  germ  cells  as  pos- 
sessing an  inherent  potentiality  which  may  institute  formative  processes;  but  the 
actual  cause  of  the  spontaneous  development  is  unexplained.  (Born,  Wilson, 
Morgan,  Driesch,  Schultze). 

Another  possible  source  of  parasitic  growths  is  suggested  by  experiments  in 
which  some  of  the  cells  during  segmentation  have  been  separated  from  the 
general  mass.  The  artificially  segregated  cells  may  develop  into  perfect  em- 
bryos smaller  than  the  normal,  or  into  partial  embryos.  Further  experiments 
along  the  same  line  on  the  frog  justify  the  assumption  that  the  segregated  cells 
or  masses  may  become  enclosed  within  the  developing  larger  embryo  and  there 
undergo  further  growth  and  differentiation  and  give  rise  to  inclusions  or 
parasites.  (Roux.) 

As  a  matter  of  fact  there  seems  to  be  no  good  reason  for  considering  any  one 
of  the  above  views  as  expressing  the  only  possibility  as  to  the  source  of  unequal 
duplicities  or  parasitic  growths.  There  is  nothing  to  show  that  all  three 
methods  may  not  contribute  to  the  various  kinds  of  duplicities  including 
certain  teratomata  of  the  sexual  glands. 

MALFORMATIONS  INVOLVING  ONE  INDIVIDUAL. 

Description,  Origin. 

While  the  more  limited  malformations  and  anomalies  affecting  individual 
organs  are  discussed  in  the  chapters  dealing  with  those  organs,  it  seems  best 
to  consider  here  some  of  the  gross  malformations  in  a  single  individual, 
especially  those  which  affect  the  external  form  of  the  body. 

DEFECTS  IN  THE  REGION  OF  THE  NEURAL  TUBE. 

The  term  cranioschisis  has  been  given  to  a  group  of  malformations,  or 
defects,  in  the  roof  of  the  skull  and  in  the  brain.  Depending  upon  the  degree 
of  defect,  the  group  is  divided  into  two  classes — acrania  and  hemicrania — • 
which  include  conditions  from  a  complete  absence  of  the  roof  of  the  skull  to 
partial  arrest  of  development.  Associated  with  these  conditions  are  varied 
defects  and  malpositions  of  parts  or  of  the  whole  of  the  brain. 

In  extensive  acrania  the  entire  roof  of  the  skull  is  lacking,  and  the  brain 
and  its  membranes  are  reduced  to  small  masses  of  tissue  lying  upon  the  floor 
of  the  skull.  The  defect  may  also  extend  to  the  cervical  vertebrae — cranio- 
rachischisis.  These  vertebrae  remain  open  dorsally  and  are  bent  inward 
(lordosis).  The  ears  are  set  upon  the  shoulders  and  the  neck  seems  to  be 
lacking. 


TERATOGENESIS.  617 

Sometimes  the  rudimentary  brain  shows  traces  of  structures  which  the 
normal  brain  possesses,  and  is  raised  above  the  level  of  the  defective  skull  like 
a  turban— acrania  with  exencephaly.  With  acrania  are  usually  associated 
facial  clefts,  defects  in  the  eyes,  etc. 

The  malformation  known  as  hemicrania  is  limited  to  a  part  of  the  skull, 
usually  the  posterior  part.  The  brain  mass  often  protrudes  through  an  opening 
in  the  cranial  vault  and  forms  a  mass  on  the  back  of  the  head  or  hanging  down 
upon  the  neck — hemicrania  with  exencephaly. 

In  the  various  forms  of  cephalocele  or  cerebral  hernia  the  roof  of  the  skull  is 
more  nearly  complete  and  the  protrusion  of  the  cranial  contents  is  limited 
to  circumscribed  areas.  The  protruding  mass  may  consist  of  brain  substance 
only — encephalocele,  or  of  the  membranes  only — meningocele,  or  of  both — 
meningoencephalocele.  Sometimes  the  brain  ventricles  are  distended  by  the 
accumulation  of  fluid — hydrencephalocele,  or  a  sac  formed  by  the  membranes 
may  be  distended  by  fluid — hydromeningocele. 

A  condition  known  as  hy-drencephaly  is  sometimes  met  with.  Fluid  ac- 
cumulates in  the  brain  cavities  after  the  skull  is  formed,  causing  a  general 
enlargement  of  both  brain  and  skull,  without  hernia  (congenital  hydrocephaly) . 

A  combination  of  hydrencephaly  and  cephalocele  may  also  occur.  The 
cervical  vertebrae  adjoining  the  skull  are  cleft  dorsally  and  the  protruding  mass 
lies  in  the  cleft — iniencephaly. 

Hydromicrencephaly  means  an  accumulation  of  fluid  with  a  rudimentary 
brain  and  a  correspondingly  small  skull. 

Porencephaly  is  a  lower  grade  of  hydromicrencephaly,  in  which  fluid  ac- 
cumulates in  the  third  and  lateral  ventricles  and  affects  the  adjacent  frontal 
and  parietal  lobes.  If  the  individual  lives  with  this  malformation,  the  intellect 
is  impaired  and  the  extremities  contract  and  atrophy. 

Microcephaly  and  micrencephaly  go  together  as  abnormal  smallness  of  the 
skull  and  brain.  The  brain,  aside  from  the  diminutive  size,  may  not  be  de- 
formed. These  conditions,  in  which  the  body  is  of  the  usual  size,  should  not 
be  confused  with  those  found  in  dwarfs  in  whom  the  body  also  is  small 
(nanocephaly). 

In  the  region  of  the  spinal  cord  there  is  a  group  of  malformations  consisting 
of  varying  degrees  of  clefts  in  the  vertebral  canal.  The  clefts  may  remain  open 
—rachischisis — or  they  may  be  covered  by  a  sac-like  prominence — spina  bifida 
(spina  bifida  cystica,  rachischisis  cystica).  Both  forms  of  cleft  may  occur  in 
any  region  of  the  vertebral  column  and  may  be  limited,  or  involve  the  entire 
column. 

The  malformation  known  as  rachischisis  appears  as  a  widely  open  groove 
bounded  laterally  by  rudimentary  laminae  of  the  vertebrae.  The  deformity  may 
include  the  entire  vertebral  column — holorachischisis,  or  it  may  be  confined  to 


618  TEXT-BOOK  OF  EMBRYOLOGY. 

a  small  part — merorachischisis,  and  is  usually  accompanied  by  curvature  of  the 
spine.  Sometimes  the  deformity  of  the  vertebral  column  is  continuous  with 
cranioschisis — craniorachischisis.  The  more  or  less  rudimentary  spinal  cord 
lies  along  the  bottom  of  the  cleft.  When  the  rachischisis  is  total  the  spinal 
cord  is  practically  wanting — amyelus. 

Spina  bifida  is  marked  by  the  presence  of  a  cyst  which  protrudes  through  a 
cleft  in  the  vertebral  column;  externally  it  presents  the  appearance  of  a  sac- 
like  structure  of  variable  size.  Three  different  types  of  spina  bifida  may  be 
recognized,  depending  upon  the  structures  involved.  If  the  cord  and  its  mem- 
branes are  included  in  the  cyst  it  is  known  as  myelomeningocele;  if  only 
the  membranes,  as  spinal  meningocele^  if  the  cord  itself  is  dilated,  as  myelo- 
cystocele. 

Myelomeningocele  is  the  most  common  form  of  spina  bifida  and  usually 
occurs  in  the  lumbo-sacral  region,  rarely  in  the  cervical  or  thoracic  region. 
Its  appearance  is  that  of  a  rounded  tumor  in  the  medial  line,  and,  if  the  child 
lives,  the  tumor  increases  in  size  and  may  become  as  large  as  a  child's  head. 
The  spinal  cord  is  bent  dorsally  and  attached  to  the  sac.  The  pia  mater  and 
arachnoid  surround  the  cord,  while  the  dura  is  incomplete.  The  spinous 
processes  and  the  adjacent  parts  of  the  arches  of  the  vertebrae  are  absent. 
From  one  to  several  vertebrae  may  be  affected. 

In  spinal  meningocele  the  spinal  membranes  bulge  out  to  form  a  sac  filled 
with  fluid.  The  vertebrae  are  not  necessarily  defective,  for  the  sac  may  pro- 
trude between  the  arches  or  through  the  intervertebral  foramina;  it  more 
often  protrudes  laterally  than  dorsally.  The  presence  of  meningocele  is 
not  at  all  incompatible  with  life,  but  the  sac  usually  enlarges  to  a  good-sized 
tumor. 

In  myelocystocele  (syringomyelocele)  the  central  canal  of  the  spinal  cord  is 
dilated  locally,  with  the  result  that  a  portion  of  the  cord  with  the  pia  and 
arachnoid  becomes  a  cystic  tumor.  It  may  occur  in  any  region,  and  is  fre- 
quently associated  writh  asymmetrical  defects  of  the  vertebral  column. 

Spina  bifida  occulta,  a  condition  in  which  neither  cleft  nor  tumor  is  visible 
externally,  is  usually  found  in  the  lumbo-sacral  region.  The  position  of  the 
defect  is  indicated  by  a  small  depressed  cicatrix  or  by  a  small  tuft  of  hair. 
The  spinal  cord  is  elongated  and  extends  into  the  sacral  canal.  The  spinal 
canal  is  sometimes  dilated  and  the  cauda  equina  affected,  in  consequence  of 
which  there  are  sensory  and  motor  disturbances  in  the  lower  extremities. 
Paralytic  club-foot  and  derangement  of  the  bladder  functions  may  result 
from  such  a  deformity  of  the  cord. 

Diastematomyelia,  or  doubling  of  the  spinal  cord,  sometimes  accompanies 
rachischisis.  The  cord  in  such  cases  is  represented  by  two  atrophic  bands. 


TERATOGENESIS.  619 

ORIGIN  OF  MALFORMATIONS  IN  THE  REGION  OF  THE  NEURAL  TUBE. 

Normally  the  neural  tube  is  formed  from  a  band  of  ectoderm  extending 
along  the  dorsum  of  the  embryonic  disk.  The  ectodermal  band  becomes 
thickened,  a  groove  appears  along  the  middle  line  and  the  margins  are  raised 
above  the  surface  of  the  embryo,  forming  the  neural  groove.  The  margins  of 
the  band  continue  to  push  upward  and  finally  meet  and  fuse  with  each  other 
throughout  their  entire  length  in  the  middorsal  line.  The  surface  ectoderm 
then  breaks  away  from  the  line  of  fusion  and  forms  a  continuous  layer  upon  the 
dorsum  of  the  embryo,  thus  leaving  the  neural  groove,  now  the  neural  tube, 
extending  the  entire  length  of  the  embryo  immediately  beneath  the  ectoderm. 

The  formation  of  the  neural  tube  is  a  fundamental  process,  occurring 
at  an  early  period.  It  is  obvious  that  any  interference  with  its  development 
will  be  followed  by  serious  defects  in  the  nervous  system  and  the  structures 
that  immediately  surround  it.  A  most  natural  result  of  such  interference  would 
be  the  failure  of  the  two  margins  of  the  neural  groove  to  unite,  and  it  is  not 
improbable  that  the  various  forms  of  cranioschisis  are  the  results  of  imperfect 
or  complete  lack  of  closure  of  the  cephalic  end  of  the  neural  groove.  Such 
failure  of  the  neural  groove  to  close  would  leave  the  dorsum  of  the  head  region 
open,  so  that  not  only  the  brain  but  also  the  cranial  vault  would  be  affected. 
If  the  failure  to  close  is  complete,  a  high  degree  of  acrania  would  result.  In 
case  of  partial  closure  some  form  of  hemicrania  might  follow. 

Rachischisis,  with  partial  or  total  absence  of  the  spinal  cord,  may  also  be 
attributed  to  defective  closure  of  the  neural  tube,  total  rachischisis  being  due  to 
complete  lack  of  closure,  partial  rachischisis  to  partial  lack  of  closure. 

The  origin  of  spina  bifida  has  been  a  much  discussed  question.  The  earlier 
view  that  the  deformity  was  due  to  accumulation  of  fluid  within  the  spinal  canal 
and  rupture  of  the  distended  sac  is  now  usually  considered  untenable.  At  the 
present  time  it  is  generally  agreed  that  spina  bifida  is  closely  related  to  defective 
closure  of  the  neural  tube,  although  the  exact  nature  of  this  relation  is  not 
known. 

According  to  one  investigator  the  defective  fusion  of  the  margins  of  the 
neural  groove  is  due  to  deficient  growth  of  the  blastoderm  (von  Reckling- 
hausen).  Another  view  is  that  the  separation  between  the  neural  tube  and 
the  adjacent  ectoderm  is  incomplete  (Torneux).  Still  another  investigator 
considers  the  defective  development  due  to  some  primary  defect  in  the  germ 
(Ziegler).  Experimental  studies  on  the  frog's  egg  suggest  to  another  observer 
that  spina  bifida  is  caused  by  defective  closure  of  the  blastopore  (Hertwig). 
Recently  it  has  become  possible  to  produce  spina  bifida  at  will  in  some  of  the 
lower  Vertebrates  (frog,  Axolotl)  by  treating  the  developing  eggs  with  a  solution 
of  sodium  chlorid  (Hertwig).  At  the  same  time  other  defects  in  the.  nervous 


620  TEXT-BOOK  OF  EMBRYOLOGY. 

system  (anencephaly)  are  produced.     In  these  experiments  the  malformations 
follow  retarded  closure  or  lack  of  closure  of  the  neural  tube. 


DEFECTS  IN  THE  REGION  OF  THE  FACE  AND  NECK,  AND  THEIR  ORIGIN. 

Associated  with  malformations  of  the  brain  there  is  a  group  of  defects  which 
involve  the  eyes  and  nose,  and  to  which  the  term  cydocephaly  has  been  applied. 
The  cerebral  hemispheres  are  derivatives  of  the  fore-brain.  Sometimes  they 
fail  to  develop  properly  and  are  represented  by  a  single  mass  occupying  a 
considerable  portion  of  the  cranial  cavity.  The  eyes  primarily  represent 
lateral,  symmetrical  outgrowths  from  the  fore-brain  vesicle.  If  the  cerebral 
hemispheres  fail  to  develop,  the  development  of  the  eyes  is  profoundly  influ- 
enced. Instead  of  being  widely  separated  there  may  be  any  degree  of  mal- 
formation from  a  mere  narrowing  of  the  distance  between  them  to  a  complete 
fusion  into  a  single  organ  within  a  single  medial  orbit — synophthalmia  or  cyclo- 
pia.  Within  this  orbit  the  eye  may  possess  double  or  partially  blended  cor- 
neae,  pupils,  lenses,  and  optic  nerves,  or  it  may  have  single  structures. 

Since  the  fronto-nasal  process,  which  plays  an  important  part  in  the  forma- 
tion of  the  nose,  depends  for  its  normal  shape  upon  the  development  of  the  fore- 
brain  region,  various  degrees  of  malformation  of  the  nose  almost  invariably 
accompany  cyclopia.  In  a  typical  cyclops  the  nose  is  reduced  to  a  fleshy  mass 
protruding  from  the  frontal  region. 

It  is  not  unusual  to  find  clefts  of  the  upper  lip  (hare  lip)  and  of  the  palate 
(cleft  palate)  associated  with  cyclopia;  for  the  normal  union  of  the  fronto- 
nasal  and  maxillary  processes  depends  upon  the  development  of  the  fore-brain 
region.  The  branchial  arches  likewise  may  be  affected  with  resulting  mal- 
formations of  the  mouth  and  external  ear.  The  two  ears  may  be  united  across 
the  ventro-medial  line — synotus  or  cydotus,  and  the  mouth  slit  may  be  absent — 
cydostomus. 

The  eye  may  also  be  the  seat  of  local  defects.  It  may  remain  abnormally 
small — microphthalmia,  or  incompletely  developed,  or  may  be  entirely  lacking 
— anophthalmia.  The  eyelids  may  enclose  an  abnormally  narrow  fissure — 
ankyloblepharon,  or  the  fissure  may  be  wanting — cryptophthalmia,  or  the  lids 
may  be  adherent  to  the  eyeball — symblepharon.  Sometimes  there  is  a  cutaneous 
fold  which  partly  fills  the  inner  canthus  like  the  nictitating  membrane  in  lower 
forms — epicanthus. 

Malformations  of  the  face  are  not  uncommon,  all  such  congenital  defects 
being  due  to  incomplete  fusion  of  the  processes  which  form  the  jaws  and 
greater  part  of  the  face  (see  page  152).  In  extreme  cases  there  is  an  early 
and  complete  arrest  of  development  of  all  the  parts  which  normally  form  the 
face — aprosopus.  Arrested  development  of  the  first  pair  of  branchial  arches 


TERATOGENESIS.  621 

results  in  abnormally  small  lower  jaws — micro  gnathy,  or  in  almost  complete 
absence  of  the  lower  jaws — agnathus;  in  the  latter  case  the  ears  are  brought 
together  in  the  ventro-medial  line — synotus.  Rarely  the  mandible  is  partly 
duplicated,  due  to  the  development  of  a  secondary  mandibular  process — 
dignathus. 

Clefts  in  the  upper  lip,  maxilla  and  palate  follow  the  lines  of  primary  union 
of  the  processes  which  form  these  structures  (consult  Figs.  136  and  137).  The 
cleft  may  affect  the  lip  alone,  may  be  single  or  double,  but  is  always  lateral— 
hare  lip  (cheiloschisis).  It  may  affect  the  lip  and  maxilla  (cheilognathoschisis), 
or  the  lip,  maxilla  and  palate  (hare  lip  and  cleft  palate,  cheilognathouranos- 
chisis).  (For  a  further  discussion  of  hare  lip  and  cleft  palate,  see  p.  216). 

Occasionally  there  is  an  entire  lack  of  union  between  the  naso-frontal  process 
and  the  maxillary  process.  The  result  is  an  oblique  cleft  which  extends  up- 
ward from  the  mouth — oblique  facial  cleft  (cheilognathoprosoposchisis).  The 
processes  which  form  the  boundaries  of  the  mouth  slit  (maxillary  and  mandib- 
ular processes)  sometimes  fail  to  fuse  to  the  normal  extent,  thus  giving  rise  to 
macrostomus;  or  the  fusion  may  proceed  beyond  the  normal  limit,  giving  rise  to 
micro stomus;  rarely  complete  fusion  of  the  processes  on  one  side  with  each  other 
and  with  their  fellows  of  the  opposite  side  results  in  closure  of  the  mouth  slit — 
astomus  or  atresia  oris.  Clefts  in  the  lower  lip,  due  to  imperfect  union  of  the 
two  mandibular  processes  in  the  medial  line,  are  rare. 

The  branchial  arches  (apart  from  the  first  which  has  already  been  con- 
sidered) and  the  branchial  grooves  are  also  subject  to  defective  developmental 
processes.  Malformations  of  the  ear,  with  closure  of  the  external  auditory 
meatus,  due  to  abnormal  development  of  the  first  groove  and  surrounding  parts, 
are  sometimes  met  with  either  alone  or  in  connection  with  other  facial  defects. 
Cervical  fistula  are  the  results  of  imperfect  closure  of  some  of  the  grooves  along 
with  rupture  of  the  membranes  that  separate  the  bottoms  of  the  external 
grooves  from  the  bottoms  of  the  internal  grooves  or  pharyngeal  pouches.  The 
fistula  may  be  complete,  that  is,  there  may  be  a  communication  between  the 
pharyngeal  cavity  and  the  exterior;  or  it  may  be  incomplete,  opening  either 
into  the  pharynx,  or  on  the  surface  of  the  body.  The  internal  opening  of  a 
cervical  fistula  is  usually  in  the  lower  part  of  the  pharynx  or  in  the  posterior 
palatine  arch  near  the  tonsil.  The  external  opening  varies  in  position.  It  is 
usually  situated  near  the  sterno-clavicular  articulation,  or  at  the  inner  or 
outer  edge  of  the  sterno-mastoid  muscle.  The  majority  of  cervical  fistulae  are 
probably  derived  from  the  second  branchial  groove.  They  all  have  the  form  of 
narrow  canals  lined  with  mucous  membrane.  Medial  cervical  fistulae,  the  ex- 
ternal openings  of  which  are  situated  in  the  medial  line,  are  rare. 

It  sometimes  happens  that  during  the  closure  of  the  branchial  grooves  por- 
tions of  the  walls  of  the  grooves  becomes  enclosed  within  the  walls  of  the 


622  TEXT-BOOK  OF  EMBRYOLOGY. 

pharynx,  that  is,  within  the  sides  of  the  neck.  This  abnormal  process  results  in 
various  forms  of  cysts  and  tumors.  The  most  common  are  simple  retention 
cysts,  known  as  branchial  or  branchio genetic  cysts,  which  vary  from  small 
insignificant  structures  to  large  tumors.  If  derived  from  the  external  branchial 
furrows,  they  are  dermoid  in  character,  lined  with  ectodermal  derivatives,  and 
contain  sebaceous  material.  If  derived  from  the  internal  furrows,  they  con- 
tain mucous  fluid,  the  lining  epithelium  is  likely  to  be  columnar  and  is  claimed 
by  some  to  be  ciliated. 

DEFECTS  IN  THE  THORACIC  AND  ABDOMINAL  REGIONS,  AND  THEIR  ORIGIN. 

As  described  elsewhere  (see  page  317),  the  digestive  tube  (primitive  gut)  and 
ventral  body  wall  are  formed  primarily  by  a  bending  ventrally  and  fusing  of  the 
originally  flat  germ  layers.  The  splanchnopleure  on  each  side  first  bends 
ventrally  and  fuses  with  its  fellow  of  the  opposite  side  in  the  medial  line  to  form 
the  gut,  and  soon  afterward  the  somatopleure  likewise  fuses  in  the  ventro- 
medial  line  to  form  the  body  wall.  Naturally  a  defective  fusion  of  the^two 
sides  of  the  somatopleure  would  result  in  a  more  or  less  extensive  medial  cleft. 
The  cleft  may  be  limited  to  a  small  portion  of  the  abdomen  or  thorax,  or  may 
extend  from  the  neck  to  the  pelvis. 

When  the  cleft  is  very  extensive  and  involves  the  thoracic  and  abdominal 
walls,  the  condition  is  known  as  thoracogastroschisis.  In  this  case  most  of  the 
viscera  protrude  through  the  cleft  (ectopia  viscerum)  and  are  covered  merely 
by  peritoneum.  Spinal  curvature  of  a  low  or  high  degree  is  usually  associated 
with  the  eventration. 

The  cleft  may  involve  the  entire  abdominal  wall — gastroschisis  completa — 
and  the  abdominal  viscera  may  protrude  through  it.  In  a  somewhat  lesser 
degree  of  fission,  parts  of  the  abdominal  viscera,  covered  with  peritoneum, 
may  protrude  and  form  what  is  known  as  omphalocele.  Not  uncommonly 
portions  of  the  intestine  and  omentum  protrude  through  an  abnormally  large 
umbilical  ring — umbilical  hernia.  The  region  below  the  umbilicus  is  not  in- 
frequently the  seat  of  fissures  in  the  abdominal  wall,  through  which  the  bladder 
may  protrude  (ectopia  vesicae).  Fissures  in  the  thoracic  wall  vary  in  extent. 
When  the  defect  is  extensive  the  heart  and  pericardium  protrude  through  the 
opening  (ectopia  cordis). 

MALFORMATIONS  OF  THE  EXTREMITIES. 

Any  degree  of  deficiency  may  exist,  from  total  absence  of  extremities  to 
the  lack  of  a  single  finger.  The  malformations,  however,  are  not  confined  to 
total  or  partial  lack  of  members,  for  supernumerary  fingers  and  toes  are  some- 
times present.  The  following  is  the  classification  given  by  Piersol: 


TERATOGENESIS.  623 

1.  One  or  More  Extremities  Wanting. — (a)  Amelus.     Both  upper  and  lower 
extremities  are  practically  absent,     (b)  Abrachius,  A  pus.     Either  the  upper  or 
lower  extremities  are  wanting,  the  other  pair  often  being  well  formed,     (c) 
Monobrachius,  Monopus.     One  upper  or  one  lower  extremity  is  absent,  the 
others  being  fully  developed. 

2.  One  or  More  Extremities  Defective. — (a)  Peromelus.     All  the  extremities 
are  imperfect.     A  striking  variety  of  this  is  the  suppression  of  the  proximal 
segments  of  the  extremities,  the  hands  and  feet  being  fairly  well  formed  (phoco- 
melus).     (b)  Perobrachius,  Per  opus.     The  former  signifies  defective  develop- 
ment of  the  upper,  the  latter  of  the  lower  extremities. 

3.  One  or  More  Extremities  Abnormally  Small  but  well  Formed. — (a)  Micro- 
melus.    All  the  extremities  are  diminutive,  but  without  any  other  malformation. 
(b)   Microbrachius,  Micropus.     One  or  both  upper  extremities  may  be  small,  or 
one  or  both  lower. 

4.  Bones  Defective  or  Absent. — Such  malformations  are  rare. 

5.  Lower  Extremities  Fused. — (a)  Sympus  (symelus  siren}.     The  lower  ex- 
tremities are  fused  more  or  less  completely,  and  the  lower  end  of  the  trunk  is 
abnormal.     The  feet  may  be  imperfect  and  double  (sympus  dipus),  or  a  single 
foot  may  be  present  (sympus  monopus),  or  the  feet  may  be  wanting  (sympus 
apus). 

6.  Hands  or  Feet  Defective. — There  is  a  great  variety  of  malformations  of  the 
hands  and  feet  due  to  arrested  development  of  some  of  the  digits.     The  varia- 
tions include  all  degrees  of  suppression  from  the  shortening  of  a  finger  or  toe  to 
almost  total  absence  of  digits.     Fusions  of  two  or  more  digits  are  not  uncom- 
mon.    Occasionally   a   structure,    suggesting  the  webs  on  the  feet  of  some 
aquatic  animals,  is  present. 

The  condition  known  as  polydactyly  (an  increase  over  the  normal  number 
of  digits)  is  occasionally  met  with.  The  increase  may  range  from  a  partial 
doubling  of  the  distal  segment  of  a  finger  or  toe  to  a  two-fold  quota  of  digits. 
Cases  of  ten  digits  are  extremely  rare,  as  are  even  cases  of  seven  or  eight.  One 
supernumerary  finger  or  toe,  rudimentary  or  complete,  is  not  uncommon.  The 
extra  digits  may  appear  on  a  single  hand  or  foot,  or  on  both  hands  or  feet,  or  on 
all  four  extremities,  not  necessarily  showing  any  symmetry.  A  statement  of  the 
possible  modes  of  origin  of  polydactyly  will  be  found  on  page  217. 

AMNIOTIC  ADHESIONS. — Many  malformations  affecting  the  embryo  or  foetus 
have  been  included  under  this  head.  It  has  been  generally  thought  that  the 
amnion  might  become  attached  to  some  part  of  the  embryo  in  such  a  way  as 
to  cause  malformations  by  interfering  with  the  normal  processes  of  growth. 
The  amnion  might  become  attached  to  the  head  and  by  interfering  with 
normal  growth  produce  hare  lip,  facial  clefts  and  generally  serious  disturb- 
ances. Undue  pressure  on  an  extremity  would  cause  it  to  be  stunted,  or 
40 


624  TEXT-BOOK  OF  EMBRYOLOGY. 

an  encircling  band  of  amniotic  tissue  might  cause  constriction  or  even  ampu- 
tation of  some  of  the  extremities,  or  of  some  of  the  digits.  Under  the  same 
head  there  might  also  be  included  certain  disturbances  possibly  caused  by  the 
umbilical  cord.  The  cord  by  becoming  wound  around  the  neck  or  extremities 
and  interfering  with  development  may  even  cause  the  death  of  the  foetus. 

Causes  Underlying  the  Origin  of  Monsters. 

Within  the  past  century  the  old  grotesque  notions  that  monsters  were  the 
results  of  supernatural  influences  or  of  sexual  congress  with  lower  animals  have 
been  overthrown  as  teratology  has  been  placed  upon  an  embryological  basis. 
The  very  old  belief  that  impressions  on  the  maternal  senses  may  influence  the 
development  of  the  embryo  is  still  held  by  those  who  possess  little  or  no  scien- 
tific knowledge,  and  is  not  uncommon  even  among  gynecologists  and  obstetri- 
cians. While  remarkable  cases  of  coincidence  have  been  recorded,  there  seems 
to  be  no  proof  whatever  that  maternal  impressions  are  reflected  upon  the  child 
in  the  uterus.  On  the  other  hand,  there  has  gradually  accumulated  a  large 
amount  of  negative  evidence  obtained  from  experimental  work.  The  results  of 
this  work  have  been  such  as  to  indicate  that  external  influences — mechanical  or 
physico-chemical — cause  the  production  of  monsters. 

Opposed  to  the  theory  that  monsters  are  due  to  external  influences  is  the 
view  that  their  cause  lies  within  the  germ,  that  is,  that  some  inherent  defect  in 
the  constitution  of  one  or  both  of  the  parental  germ  cells  is  brought  out  in  the 
new  organism  that  develops  after  their  union.  According  to  this  theory, 
therefore,  heredity  is  the  important  factor  in  teratogensis.  While  the  oc- 
currence of  defective  conditions  in  the  germ  cells  cannot  be  demonstrated,  the 
apparent  influence  of  heredity  in  the  production  of  malformations  has  long  been 
recognized.  Certain  malformations,  even  so  great  as  to  put  the  embryo  or 
foetus  in  the  class  of  monsters,  have  been  known  to  occur  in  families  through 
successive  generations.  Such  cases  may  be  mere  coincidences,  yet  more  prob- 
ably they  are  indicative  of  hereditary  influence. 

All  the  theories,  therefore,  are  concerned  with  the  question  "whether  the 
conditions  that  produce  a  monster  are  germinal  and  hereditary  or  are  external  influ- 
ences.  acting  upon  a  normal  germ"  (Mall).  Some  defend  the  germinal  or 
hereditary  factor  as  the  most  potent  cause  in  the  production  of  malformations, 
while  others  just  as  strongly  advocate  the  view  that  normal  or  abnormal 
development  depends  largely  upon  external  factors.  It  does  not  seem  possible 
to  deny  the  importance  of  heredity  in  the  development  of  the  normal  organism; 
nor,  on  the  other  hand,  can  the  importance  of  external  influence,  of  environ- 
ment, upon  normal  development  be  denied.  The  same  factors  may  be  con- 
sidered as  active  in  abnormal  development,  and  it  does  not  seem  that  either 


TERATOGENESIS.  625 

factor  can  reasonably  be  considered  as  the  only  cause  in  the  production  of 
malformations.  Granting,  however,  that  both  hereditary  and  external  influ- 
ences are  at  work  in  the  production  of  monsters,  it  is  still  difficult  to  determine 
the  separate  role  of  each  factor;  on  the  one  hand,  either  influence  may  appear 
capable  of  having  produced  some  given  anomaly;  on  the  other,  both  of  them 
may  have  been  responsible  for  its  appearance. 

The  first  phase  of  the  theory  of  external  influence  was  presented  three- 
quarters  of  a  century  ago  when  attempts  were  made  to  produce  monsters.  The 
experiments  led  to  the  formulation  of  the  mechanical  theory,  which,  when  applied 
to  human  monsters,  considers  them  as  the  results  of  mechanical  influences  upon 
the  embryo,  such  as  the  pressure  caused  by  tight  lacing  or  by  contractions  of  the 
uterus.  This  theory  was  gradually  transformed  into  the  view  that  amniotic 
bands  compress  or  constrict  the  embryo,  thus  bringing  about  malformations. 
In  its  turn  the  latter  supposition  has  recently  been  criticized  and  the  view  sub- 
stituted that  the  amniotic  adhesions  are  the  results  of  malformations  and  not 
the  cause  of  them  (Mall). 

The  theory  of  external  influence  seems  recently  to  be  losing  ground  in  favor 
of  the  physico-chemical  theory.  The  latter  has  gradually  been  evolved  during 
the  course  of  a  great  number  of  experiments  on  the  production  of  malformations 
and  monsters  among  the  lower  forms  of  animals.  It  has  gained  ground  because 
certain  definite  malformations  have  been  obtained  by  subjecting  the  living  egg 
or  young  embryo  to  unusual  conditions.  The  experiments  consist  of  interfering 
in  some  way  with  the  normal  course  of  development.  The  interference  may  be 
mechanical  or  chemical,  or  both,  but  is  always  of  such  a  nature  as  to  cause  the 
egg  or  embryo  to  develop  under  unnatural  conditions — either  in  an  unnatural 
environment  or  after  having  had  some  of  its  own  substance  wholly  or  partly 
removed.  The  results  obtained,  the  strange  creatures  which  develop  after 
such  interference,  are  not  infrequently  comparable  with  malformations  and 
monsters  found  among  the  higher  animals,  and  they  strongly  suggest  that  mal- 
formations among  the  higher  forms  of  animal  life  are  the  results  of  similar  in- 
terference with  the  normal  course  of  development  of  the  egg. 

THE  PRODUCTION  OF  DUPLICATE  (OR  POLYSOMATOUS)  MONSTERS. — By 
shaking  sea-urchin  ova  when  in  the  two-cell  stage  so  that  the  blastomeres  are 
separated,  each  blastomere  can  be  made  to  grow  into  a  whole  embryo.  De- 
pending upon  the  degree  of  separation,  the  two  embryos  will  be  separate  or  more 
or  less  united  forming  a  double  monster.  If  sea-urchin  ova  are  placed  in  a 
mixture  of  equal  parts  sea-water  and  distilled  water  shortly  after  fertilization, 
the  cell  membranes  rupture  and  part  of  the  protoplasm  bulges  out.  When  the 
ova  are  replaced  in  normal  sea-water  cleavage  begins  and  one  of  the  two  primary 
nuclei  wanders  into  the  extruded  protoplasm.  Each  nucleus  with  its  proto- 
plasm becomes  an  embryo,  and  the  result  is  a  double  monster.  If  the  outflow  of 


626  TEXT-BOOK  OF  EMBRYOLOGY. 

protoplasm  originally  occured  in  several  places,  each  droplet  produces  an 
embryo  and  the  result  is  a  triple  or  quadruple  monster  (Loeb) . 

Similar  experiments  have  also  been  performed  on  Vertebrates.  For  example, 
the  two  primary  blastomeres  of  Amphioxus  have  been  partly  separated  and 
double  monsters  developed.  The  blastomeres  in  the  four-cell  stage  have  been 
incompletely  separated,  resulting  in  double  embryos  of  equal  size,  or  triple 
embryos,  or  quadruple  monsters.  Frog's  eggs  have  been  made  to  produce 
double  monsters  by  keeping  them  turned  upside  down  after  the  morula  stage; 
the  same  result  has  also  been  produced  by  loosely  tying  a  ligature  in  the  furrow 
between  the  two  primary  blastomeres.  A  most  curious  result  has  been  obtained 
by  splitting  the  limb  bud  of  a  growing  tadpole  one  or  more  times.  Two  or  even 
a  cluster  of  limbs  may  develop  where  only  one  does  normally  (Tornier) . 

These  few  examples  from  the  great  number  of  experiments  which  have  been 
performed  serve  to  show  that  great  light  can  be  thrown  upon  the  problems  of 
teratogenesis  by  experimental  embryology.  While  they  do  not  prove  that  there 
are  no  other  possible  modes  of  origin  for  malformations,  they  indicate  the  im- 
portance of  external  influences  upon  development,  and  afford  tangible  evidence 
in  the  study  of  monsters. 

THE  PRODUCTION  OF  MONSTERS  IN  SINGLE  EMBRYOS. — In  single  embryos 
of  the  lower  forms  it  is  possible  to  produce  by  various  means  a  great  variety  of 
malformations,  many  of  which  are  likewise  comparable  with  malformations 
found  in  human  embryos.  By  placing  recently  fertilized  eggs  of  Fundulus 
in  a  1.5  per  cent,  aqueous  solution  of  potassium  chlorid,  embryos  may  be 
produced  in  which  the  heart  is  developed  but  does  not  beat,  and  in  which  the 
blood  vessels  appear  in  their  normal  positions  but  with  irregular lumina  (Loeb). 
After  extirpating  the  heart  anlage  from  very  young  frog  embryos,  the  latter  grow 
irregularly  and  become  edematous;  the  larger  vascular  trunks  are  distended, 
but  the  capillary  system  is  imperfect  or  absent,  and  the  development  of  many 
other  organs  is  inhibited  (Knower.)  Similar  results  may  be  obtained  by 
placing  the  young  embryos  in  aceton-chloroform  which  inhibits  the  heart 
action. 

It  is  possible  to  produce  typical  spina  bifida  in  frog  embryos  by  putting 
them,  during  the  early  stages  of  development,  into  a  0.6  per  cent,  solution  of 
sodium  chlorid  (Morgan  and  Tsuda).  If  the  eggs  of  Axolotl  are  treated  with 
a  0.7  per  cent,  solution  of  sodium  chlorid  all  the  embryos  have  spina  bifida 
(Hertwig).  If  the  eggs  of  Fundulus  are  placed  in  a  solution  of  magnesium 
chlorid,  50  per  cent,  of  them  produce  embryos  with  cyclopia  (Stockard). 

Even  these  few  examples  from  the  enormous  number  of  experiments  that 
have  been  tried  in  the  study  of  single  monsters  again  lead  to  the  conclusion  that 
at  least  some  malformations  in  single  individuals  are  due  to  external  influences 
and  not  to  germinal  defects. 


TERATOGENESIS.  627 

THE  SIGNIFICANCE  OF  THE  FOREGOING  IN  EXPLAINING  THE  PRODUCTION 
OF  HUMAN  MONSTERS. — There  is,  of  course,  no  way  to  obtain  experimental 
evidence  for  or  against  any  theory  so  far  as  the  human  subject  is  concerned. 
But  it  is  possible  to  compare  the  results  of  experiments  on  the  lower  animals 
with  condions  found  in  human  embryos.  So  many  malformed  human  embryos 
resemble  in  a  general  way  and  often  in  detail  the  monsters  in  the  lower  forms 
produced  by  experimental  means  that  a  probable  similarity  in  the  causation 
of  them  at  once  suggests  itself.  The  monsters  in  the  lower  forms  are  artifici- 
ally produced  by  interfering  with  the  normal  course  of  development  of  the 
egg,  and  by  disturbing  the  normal  conditions  of  nutrition  and  growth.  The 
disturbing  factors  are  mechanical  or  chemical,  or  both. 

According  to  the  recent  opinion  of  Mall,  the  primary  disturbing  factors  in 
man  are  not  poisons  in  the  maternal  blood,  corresponding  with  chemical  agents 
used  in  experiments,  but  the  faulty  implantation  of  the  ovum  in  the  uterine 
mucosa.  This  means  that,  after  the  fertilized  and  segmenting  ovum  has 
passed  down  the  oviduct  and  entered  the  uterus,  it  fails  to  become  properly 
embedded  in  the  mucous  membrane.  The  immediate  result  is  an  imperfect 
formation  of  the  fcetal  coverings,  especially  of  the  chorion. 

The  reasons  for  the  faulty  implantation  are  not  clear,  but  they  are  possibly, 
even  probably,  to  be  found  in  the  condition  of  the  uterus.  The  most  plausible 
explanation  is  that  some  form  of  endometritis  makes  the  uterine  mucosa  in- 
capable of  properly  adapting  itself  for  the  reception  of  the  ovum. 

In  the  case  of  the  human  embryo,  such  an  imperfection  in  the  agency  through 
which  it  receives  its  nourishment  might  be  considered  in  a  sense  analogous  to 
the  external  influences  that  produce  monsters  in  the  lower  forms. 


References  for  Further  Study. 

AHLFELD,  F.:  Die  Missbildungen  des  Menschen.     Leipzig,  1880-1882. 

AHLFELD,  F.:  Lehrbuch  der  Geburtshilfe.     Leipzig,  1903. 

BALLANTYNE,  J.  W.:  Antenatal  Pathology.  2  Vols.     Edinburgh,  1904. 

BARDEEN,  C.  R.:  Abnormal  Development  of  Toad  Ova  Fertilized  by  Spermatozoa 
exposed  to  the  Roentgen  Rays.  Jour,  of  Exp.  Zool.,  Vol.  IV,  1907. 

BEARD,  J.:  The  Morphological  Continuity  of  the  Germ  Cells  in  Raja  batis.  Anat. 
Anz.,  Bd.  XVIII,  1900. 

CONKLIN,  E.  G.:  The  Cause  of  Inverse  Symmetry.     Anat.  Anz.,  Bd.  XXIII,  1903. 

DARESTE,  C.:  Recherches  sur  la  production  des  monstrosites.     Paris,  1891. 

DRIESCH,  H.:  Entwickelungsmechanische  Studien.  Zeitschr.  j.  wissensch.  Zool.,  Bd. 
LIII,  Bd.  LV. 

FORSTER,:  Die  Missbildungen  des  Menschen.     Jena,  1865. 

HERTWIG,  O.:  Urmund  und  Spina  bifida.     Arch.  f.  mik.  Anat.,  Bd.  XXXIX,  1892. 

HERTWIG,  O.:  Die  Entwickelung  des  Froscheies  unter  dem  Einfluss  schwacherer  und 
starkerer  Kochsalzlosungen.  Arch.  j.  Mik.  Anat.,  Bd.  XLIV,  1895. 


628  TEXT-BOOK  OF  EMBRYOLOGY. 

HERTWIG,  O.:  Missbildungen  und  Mehrfachbildungen.  In  Hertwigs  Handbuch  der 
•vergleich.  u.  experiment.  Entwickelungslehre  der  Wirbeltiere,  Bd.  I,  Teil  I,  1903. 

HIRST  AND  PIERSOL:  Human  Monsters.     Philadelphia,  1891. 

KNOWER,  H.  McE.:  Effects  of  Early  Removal  of  the  Heart  and  Arrest  of  the  Circulation 
on  the  Development  of  Frog  Embryos.  Anat.  Record  Vol.  VII,  1907. 

LOEB,  J.:  Beitrage  zur  Entwickelungsmechanik  der  aus  einem  Ei  entstehenden  Doppel- 
bildungen.  Roux's  Arch.  }.  Entwickelungsmechanik  der  Organismen,  Bd.  I,  1895. 

LOEB,  J.:  Studies  in  General  Physiology.     Chicago,  1905. 

MALL,  F.  P. :  A  Study  of  the  Causes  Underlying  the  Origin  of  Human  Monsters.  Jour, 
oj  Morphol,  Vol.  XIX,  1908. 

MARCHAND,  L.:  Missbildungen.  In  Eulenburg's  Real-Encyclopadie  der  gesammten 
Heilkunde,  Bd.  XV,  1897. 

MORGAN,  T.  H. :  Half-embryos  and  whole  Embryos  from  one  of  the  first  two  Blastomeres 
of  the  Frog's  Egg.  Anat.  Anz.,  Bd.  X,  1895. 

MORGAN,  T.  H.:  Ten  Studies  in  Roux's  Arch.  /.  Entwickelungsmechanik  der  Organ- 
ismen, Bd.  XV-XIX,  1902-1905. 

PANUM:  Entstehung  der  Missbildungen.     Berlin,  1880. 

PIERSOL,  G.  A.:  Teratology.  In  Wood's  Reference  Handbook  of  the  Medical  Sciences, 
Vol.  VII,  1904. 

SCHULTZE,  O.:  Die  kiinstliche  Erzeugung  von  Doppelbildungen  bei  Froschlarven  mit 
Hilfe  abnormer  Gravitationswirkung.  Roux's  Arch.  /.  Entwickelungsmechanik  der 
Organismen,  Bd.  I,  1895. 

SCHWALBE,  E.:  Die  Morphologic  der  Missbildungen  des  Menschen  und  der  Thiere. 
Jena,  1906-1907. 

STOCKARD,  C.  R.:  The  Artificial  Reproduction  of  a  Single  Median  Cyclopean  Eye  in 
the  Fish  Embryo  by  Means  of  Sea-water  Solutions  of  Magnesium  Chlorid.  Roux's  Arch.  }. 
Entwickelungsmechanik  der  Organismen,  Bd.  XXIII,  1907. 

TORNIER,  G.:  An  Knoblauchskroten  experimentell  entstandene  iiberzahlige  Hinter- 
gliedmassen.  Roux's  Arch  /.  Entwickelungsmechanik  der  Organismen,  Bd.  XX,  1905. 

WILDER,  H.  H.:  Duplicate  Twins  and  Double  Monsters.  American  Jouc.  oj  Anat., 
Vol.  Ill,  1904. 

WILLIAMS,  J.  W.:  Obstetrics.     New  York,  1903. 

WILSON,  E.  B.:  On  Multiple  and  Partial  Development  in  Amphioxus.  Anat.  Anz., 
Bd.  VII,  1893. 


APPENDIX. 


General  Technic. 
I.  PROCURING  AND  HANDLING  MATERIAL.* 

Methods  of  procuring  and  treating  material  for  the  study  of  maturation,  fertilization 
and  segmentation  are  given  under  "Practical  Suggestions"  at  the  ends  of  the  chapters  treating 
of  those  subjects  (pp.  33,  41  and  53,  respectively). 

AMPHIBIAN  EMBRYOS. — The  eggs  of  the  common  wood  frog  (Rana  sylvatica)  can  be 
found  in  ponds  during  the  first  few  warm  days  of  spring  (usually  the  latter  part  of  March  in 
the  vicinity  of  New  York  City).  When  deposited,  the  eggs  are  embedded  in  a  compact  mass 
of  transparent  gelatinous  substance.  After  lying  in  the  water  for  a  few  hours,  this  substance 
swells  so  that  each  egg  appears  to  be  surrounded  by  its  own  little  spherical  mass;  all  the  masses, 
however,  still  clinging  together  to  form  a  cluster. 

The  eggs  are  fertilized  soon  after  being  deposited,  the  spermatozoa  floating  free  in  the 
water,  and  within  a  few  hours  begin  to  segment.  The  stage  of  segmentation  can  usually 
be  discerned  with  the  naked  eye,  but  it  is  always  well  to  be  provided  with  a  hand  lens. 

If  the  eggs  are  to  be  used  for  gross  study,  the  clusters  should  be  put  into  a  large  quantity 
of  4  per  cent,  formalin.  Stronger  formalin  will  render  the  gelatinous  substance  opaque. 
The  eggs  can  be  preserved  in  this  fluid  indefinitely. 

The  later  stages  of  cleavage  and  the  young  embryos  can  also  be  obtained  in  ponds,  but 
it  is  usually  more  convenient  to  take  a  number  of  the  clusters  to  the  laboratory  in  water. 
If  the  water  is  kept  fresh,  development  goes  on  almost  as  well  as  in  the  natural  surroundings. 
In  this  way  it  is  possible  to  obtain  whatever  stages  are  desired. 

If  the  eggs  or  young  embryos  are  to  be  used  for  the  study  of  finer  structures  in  sections, 
Flemming's  fluid  is  one  of  the  best  fixatives.  The  spherules  of  gelatinous  substance  should 
be  cut  apart,  however,  before  fixing.  After  the  embryos  have  grown  to  a  length  of  3  or  4  mm., 
the  gelatinous  substance  is  easily  removed  before  fixing.  During  the  cleavage  stages,  how- 
ever, the  removal  is  a  difficult  but  necessary  procedure,  either  before  or  after  fixation.  One 
of  the  best  methods  is  to  dissolve  the  capsules  with  some  fluid  which  does  not  injure  the  eggs. 
Put  the  fixed  eggs  in  a  10  per  cent,  solution  of  sodium  hypochlorite  diluted  with  5  to  6  volumes 
of  water  and  leave  them  until  they  can  be  shaken  free  (several  minutes  or  longer).  The 
following  method  is  one  of  the  most  successful.  Cut  the  fresh  spherules  from  the  general 
mass  and  put  for  several  hours  in 

Saturated  solution  picric  acid  in  35  per  cent,  alcohol .    .   100  volumes. 

Sulphuric  acid 2  volumes. 

Wash  for  several  hours  in  graded  alcohols  up  to  70  per  cent.     If  left  for  three  or  four  days 
in  the  70  per  cent,  alcohol,  the  capsule  swells  and  can  be  picked  off  with  needles.     The 

*  Embryolo?ical  material  can  also  be  purchased  at  Johns  Hopkins  University,  at  the  South 
Harpswell  Laboratory  (Prof.  J.  S.  Kingsley,  Tufts  College,  Mass.),  and  at  the  Marine  Biological 
Laboratory  (Mr.  George  M.  Gray,  Woods  Hole,  Mass.).  Models  of  embryos  and  developing  parts 
are  always  of  great  assistance  to  the  student  and  teacher.  These  can  be  obtained  from  firms  deal- 
ing in  scientific  apparatus. 

629 


630  APPENDIX. 

eggs  may  be  preserved  in  80  per  cent,  alcohol  and  are  then  ready  for  dehydration  and 
embedding. 

On  account  of  the  yolk,  amphibian  eggs  are  very  brittle  when  embedded  in  paraffin, 
thus  making  section  cutting  difficult.  This  difficulty  can  be  overcome  to  a  great  extent 
by  the  following  method.  After  cutting  a  section,  paint  a  coat  of  very  thin  celloidin  over  the 
cut  surface  of  the  block  of  paraffin.  The  celloidin  should  be  so  thin  that  the  surface  does 
not  appear  glossy  after  drying.  Let  the  celloidin  harden  for  a  few  seconds,  and  then  cut 
the  next  section.  If  this  method  is  followed,  it  is  possible  to  cut  ribbons  of  sections  as  usual, 
while  at  the  same  time  each  section  is  kept  from  breaking  by  the  film  of  celloidin.  The 
sections  are  afterward  treated  as  ordinary  paraffin  sections. 

CHICK  EMBRYOS. — With  an  incubator,  chick  embryos  are  obtainable  in  any  stage  and 
number,  and  afford,  for  the  study  of  various  structures,  material  which  is  otherwise  difficult 
or  impossible  to  secure.  Care  should  be  taken  to  obtain  eggs  that  are  fresh  and  fertile. 
The  time  should  be  marked  on  the  eggs  when  they  are  put  in  the  incubator.  The  student 
should  begin  with  the  later  stages  since  these  are  more  easily  handled. 

Removing  the  embryos  from  the  eggs,  especially  the  younger  stages,  requires  great  care, 
but  should  be  done  as  speedily  as  possible.  Prepare  a  basin  of  normal  salt  solution  warmed 
to  a  temperature  of  40°  C.  (104°  F.).  Take  an  egg  from  the  incubator  and  allow  it  to  lie  in 
one  position  for  a  minute  or  two  in  order  to  allow  the  side  of  the  yolk  containing  the  embryo 
to  come  uppermost.  Carefully  break  or  cut  a  hole  an  inch  in  diameter  in  the  shell.  If  any  of 
the  white  of  the  egg  overflows,  snip  it  off  with  scissors,  otherwise  it  will  cause  the  yolk  to  roll 
over.  The  germinal  area  or  embryo  can  be  seen  lying  on  the  top  of  the  yolk.  Immerse  the 
egg  in  the  warm  salt  solution.  Insert  one  blade  of  the  scissors  into  the  yolk  just  beyond 
the  edge  of  the  germinal  area  and  cut  rapidly  around  the  area  until  a  circular  incision  is 
completed.  Take  up  the  edge  of  the  germinal  area  with  a  pair  of  fine  forceps  and  gently  pull 
it  free  from  the  yolk.  A  little  yolk  may  cling  to  the  lower  surface,  but  this  can  usually  be 
removed  by  gentle  shaking  in  the  salt  solution.  Then  with  a  glass  slide  transfer  the 
embryo  to  the  fixing  fluid.  Care  should  be  taken  that  the  blastoderm  is  flat  when  it  goes 
into  the  fixative. 

For  chick  embryos  of  the  first  or  second  day  of  incubation,  Zenker's  or  Flemming's  fluid 
is  perhaps  the  best  fixative.  With  Zenker's,  fixation  is  complete  in  from  2  to  4  hours;  with 
Flemming's  a  little  longer  time  is  necessary.  Wash  in  running  water  for  an  hour,  or  in  several 
changes  of  water  for  the  same  length  of  time.  Harden  in  graded  alcohols  (30  per  cent., 
50  per  cent.,  and  70  per  cent.,  an  hour  or  more  in  each)  and  preserve  in  80  per  cent,  alcohol. 

For  embryos  of  more  than  two  days'  incubation,  Zenker's  or  Bouin's  fluid  is  a  good 
fixative.  The  time  required  for  fixation  (6  hours  or  more)  varies  with  the  size  of  the  speci- 
men. After  Bouin's  fluid,  several  changes  of  from  30  per  cent,  to  50  per  cent,  alcohol, 
instead  of  water,  should  be  used  for  washing. 

MAMMALIAN  EMBRYOS. — Pig  embryos  can  be  obtained  at  an  abattoir  in  considerable 
numbers  and  with  but  little  expense,  and  consequently  yield  some  of  the  best  mammalian 
material  for  embryological  purposes.  It  is  necessary  to  ask  merely  that  the  man  who  removes 
the  viscera  lay  aside  such  uteri  as  appear  distended.  Owing  to  precocious  development  of 
the  chorionic  vesicle,  a  uterus  containing  embryos  of  6  mm.  or  larger  will  be  noticeably 
swollen.  Cut  the  uterus  open  by  a  longitudinal  incision  as  soon  as  possible.  With  the  aid 
of  scissors,  fine  forceps  and  a  horn  spoon,  carefully  remove  the  embryos  and  transfer  them 
immediately  to  the  fixing  fluid. 

Embryos  up  to  35  or  40  mm.  can  be  fixed  in  toto  in  Zenker's  or  Bouin's  fluid.  They 
should  remain  in  the  fixative  from  8  hours  (embryos  of  6  mm.)  to  48  hours  (embryos  of 


APPENDIX.  63i 

40  mm.).  Larger  embryos  should  be  opened  by  a  ventral  incision  to  allow  the  fixative  to 
penetrate;  or  portions  may  be  removed  and  fixed  as  desired.  Flemming's  fluid  is  an  excellent 
fixing  agent  for  small  pieces  of  tissue. 

After  Zenker's  or  Flemming's  fluid,  the  specimen  should  be  washed  in  running  water 
for  a  few  hours  and  then  hardened  in  graded  alcohols  to  80  per  cent,  and  preserved  in  the 
latter.  After  Bouin's  fluid,  the  washing  should  be  done  in  several  changes  of  the  weaker 
alcohols  instead  of  water. 

With  some  extra  facilities  and  trouble,  rabbit  embryos  also  are  available.  Furthermore, 
it  is  possible  to  obtain  very  early  stages.  The  female  rabbit  should  be  allowed  to  become 
pregnant  and  then  be  isolated  until  she  gives  birth  to  her  young  The  date  of  birth  should 
be  noted  and  30  days  later  the  male  should  be  admitted  and  the  exact  time  of  coitus  recorded. 
At  any  time  thereafter,  the  time  depending  upon  the  stage  desired,  the  animal  is  killed  and 
the  uterus  and  oviducts  at  once  removed.  Up  to  and  including  the  third  day  after  coitus, 
the  ova  are  in  the  oviducts.  They  may  be  found  by  injecting  a  weak  solution  of  osmic  acid 
(o.i  per  cent.)  into  the  oviduct  with  a  small  syringe,  collecting  the  liquid  that  escapes  in  a 
series  of  watch  glasses  and  examining  it  under  the  microscope.  Or  the  oviducts  may  be 
fixed,  hardened  and  embedded  in  toto  and  cut  into  serial  sections. 

During  the  fourth,  fifth  and  sixth  days  the  ova  lie  free  in  the  cavity  of  the  uterus.  The 
uterus  should  be  opened  carefully  with  fine  scissors.  The  ova  are  small  rounded  bodies 
with  pearly  luster.  They  can  be  examined  in  some  "indifferent"  medium,  such  as  the 
peritoneal  fluid  of  the  mother,  or  blood  serum.  After  the  sixth  day  the  ova  become  attached 
to  the  uterine  mucosa.  A  little  block  of  the  wall  of  the  uterus  containing  the  ovum  can  be 
cut  out  and  fixed  in  Flemming's  or  Zenker's  fluid. 

The  way  in  which  human  embryos  are  usually  obtained  and  the  methods  of  treating  them 
are  discussed  on  p.  159  et  seq. 

II.  FIXATION. 

Embryonic  tissues  are  soft  and  delicate  and  should  be  treated  with  reagents  which  cause 
as  little  shrinkage  or  swelling  as  possible.  The  embryos  should  be  fresh  and  should  not  be 
handled  more  than  is  absolutely  necessary  before  fixing.  Large  quantities  of  the  fixative 
should  be  used,  at  least  ten  times  the  volume  of  the  object  to  be  fixed.  For  ordinary  histologi- 
cal  study,  the  fixative  used  should  be  of  such  a  nature  thai  the  tissues  will  afterward  take  a 
good  differential  stain.  Bouin's,  Zenker's  and  Orth's  fluids  are  good,  and  prepare  the 
tissues  for  a  brilliant  haematoxylin  and  eosin  stain.  Flemming's  fluid  (for  small  pieces  of 
tissue)  gives  an  excellent  fixation,  and  can  be  followed  most  satisfactorily  by  Heidenhain's 
iron-haematoxylin.  For  special  purposes,  special  fixatives  and  stains  are  necessary.  The 
fixatives  which  perhaps  give  the  best  results  with  certain  structures  are  given  in  "Practical 
Suggestions"  in  the  chapters  treating  of  those  structures.  The  formulas  and  some  general 
directions  are  given  below. 

1.  Alcohol. — Strong  alcohol  (95  per  cent.)  may  be  used  when  no  other  fixative  is  at  hand, 
but  always  causes  considerable  shrinkage.     It  is  sometimes  convenient  to  use  for  fixing  small 
human  embryos  with  the  membranes  intact  (see  "Practical  Suggestions,"  p.  159). 

2.  Bourn's  fluid. — 

Picric  acid,  saturated  aqueous  solution 75  parts. 

Formalin  (commercial) 25  parts. 

Acetic  acid 5  Parts- 

This  fluid  has  good  penetrating  powers,  fixes  both  nuclear  and  cytoplasmic  structures 
well,  and  causes  no  shrinkage.  Embryos  35  to  40  mm.  long  are  fixed  in  from  24  to  36 


632  APPENDIX. 

hours;  smaller  ones  in  less  time.  After  fixation,  the  specimens  should  be  washed  in  several 
changes  of  30  to  50  per  cent,  alcohol,  but  not  in  water.  A  few  drops  of  ammonia  added  to 
the  alcohol  will  facilitate  the  removal  of  the  picric  acid.  Tissues  thus  treated  will  take  a 
brilliant  differential  stain  (Weigert's  hsematoxylin,  followed  by  eosin  or  acid  fuchsin). 
Bouin's  fluid  is  also  an  excellent  decalcifying  agent  (see  technic,  p.  218). 

3.  Camay1  s  fluid. — 

Glacial  acetic  acid i  part. 

Absolute  alcohol 6  parts. 

Chloroform 3  parts. 

This  is  one  of  the  quickest  and  most  penetrating  fixatives  and  prepares  the  tissues  for  almost 
any  stain  desired.  It  has  been  used  with  success  in  studying  developing  muscle  (see  p.  315). 
Wash  with  alcohol  instead  of  water 

4.  Flemming1  s  fluid. — 

1  per  cent,  chromic  acid 15  parts. 

2  per  cent,  osmic  acid       4  parts. 

Glacial  acetic  acid i  part. 

The  solution  should  be  freshly  made.  It  is  perhaps  the  best  fixative  for  nuclear  structures, 
but  has  the  disadvantage  of  poor  penetration.  The  objects  to  be  fixed  should  not  be  more 
than  a  quarter  of  an  inch  thick,  and  less  if  possible.  Specimens  should  remain  in  the  fluid 
for  24  hours  or  longer.  They  are  then  washed  in  running  water  for  several  hours  and  trans- 
ferred to  graded  alcohols  up  to  80  per  cent. 

5.  Formalin. — Dilute  i  volume  of  commercial  formalin  with  9  volumes  of  water.     (Com- 
mercial formalin  is  a  40  per  cent,  solution  of  formaldehyde  gas  in  water.)     This  diluted 
fluid  is  usually  called  4  per  cent,  formalin,  although  strictly  speaking,  it   is  4   per  cent, 
formaldehyde. 

Formalin,  in  the  solution  mentioned  above,  can  be  used  as  a  fixative  with  fairly  good 
results.  It  has  the  advantage  of  great  penetrating  power  and  consequently  can  be  used  with 
large  embryos.  The  specimens  may  remain  in  the  fluid  several  days  and  should  then  be 
carried  through  graded  alcohols  up  to  80  per  cent. 

6.  Gilson's  fluid. — 

Absolute  alcohol      i   part. 

Glacial  acetic  acid i  part. 

Chloroform i  part. 

Mercuric  chloride to  saturation. 

This  is  a  very  rapid  fixative,  and  is  much  used  for  fixing  objects  that  are  highly  impenetrable 
Whole  oviducts  of  Ascaris,  for  example,  are  fixed  in  from  15  to  30  minutes  (see  p.  33). 
Specimens  should  afterward  be  washed  in  several  changes  of  70  per  cent,  alcohol  containing 
a  few  drops  of  tincture  of  iodine. 

7.  Orth's  fluid  (Formalin-Mutter's  fluid). — 

Potassium  bichromate      5  grms. 

Sodium  sulphate       2  grms. 

Water          100  c.c. 

Formalin,  8  per  cent 100  c.c. 

This  is  a  combination  of  equal  parts  of  double  strength  Miiller's  fluid  and  8  percent,  for- 
malin. The  two  should  be  mixed  just  before  using.  It  is  one  of  the  best  general  fixatives 


APPENDIX. 


633 


with  good  penetrating  power.  Fixation  is  complete  in  from  24  to  48  hours  Wash  in  run- 
ning water  a  few  hours,  then  transfer  to  graded  alcohols.  The  tissues  take  a  good  differen- 
tial stain  (haematoxylin  and  eosin). 

8.  Perenyi's  fluid. — 

Nitric  acid,  10  per  cent 4  parts. 

Alcohol      3  parts- 

Chromic  acid,  0.5  per  cent ,  parts. 

Small  embryos  are  fixed  in  from  6  to  12  hours.  Wash  in  several  changes  of  70  per  cent, 
alcohol  (24  hours)  and  preserve  in  80  per  cent,  alcohol.  This  fixative  is  claimed  to  be  espe- 
cially good  for  segmenting  ova. 

9.  Zenker's  fluid. — 

Potassium    bichromate 2.5  grams. 

Sodium    sulphate      i  gram. 

Mercuric    chloride 5  grams. 

Glacial  acetic  acid 5  c.c. 

Water 100  c.c. 

This  should  be  freshly  made  or  the  acetic  acid  added  to  a  stock  solution  of  the  other  ingre- 
dients just  before  using.  This  is  a  good  fixative  for  both  nuclei  and  cytoplasm,  but  has  a 
tendency  to  cause  shrinkage.  Fixation  of  small  embryos  (up  to  20  mm.)  is  complete  in  from 
12  to  24  hours.  Wash  in  running  water  for  12  hours  and  transfer  to  70  per  cent,  or  80  per 
cent,  alcohol.  The  mercuric  chloride  always  forms  precipitates  in  the  tissues,  but  these 
can  usually  be  removed  by  adding  a  little  tincture  of  iodine  to  the  alcohol  from  time  to  time 
until  the  alcohol  retains  the  iodine  color.  Then  change  to  fresh  alcohol. 

III.  HARDENING. 

.Although  most  fixatives  tend  to  harden  the  tissues,  it  is  almost  always  necessary  to 
harden  them  further.  For  this  purpose  alcohol  is  used.  With  delicate  tissues  it  is  advisa- 
ble to  use  grades  of  30,  50,  70,  and  80  per  cent.,  leaving  the  specimen  in  each  grade  for 
several  hours. 

IV.  PRESERVATION. 

Alcohol  (70  to  80  per  cent.)  is  much  used  as  a  preserving  fluid.  After  several  months,  how- 
ever, tissues  are  likely  to  lose  their  staining  qualities  to  some  extent.  A  better  preserving 
fluid,  in  which  specimens  may  remain  almost  indefinitely,  is  made  of  equal  parts  alcohol  (95 
per  cent.)  glycerin  and  water.  Objects  fixed  in  formalin  may  be  preserved  in  the  formalin 
and  then  passed  through  the  graded  alcohols  in  preparation  for  embedding. 

V.  EMBEDDING. 

Paraffin  should  be  used  for  small  objects  or  when  serial  sections  are  to  be  cut.  Celloidin 
is  very  convenient  for  larger  specimens,  especially  when  a  large  number  of  sections  is  to  be 
cut  for  class  purposes. 

Celloidin  embedding.  Place  the  hardened  specimen  in  95  per  cent,  alcohol  for  24  hours, 
and  then  in  equal  parts  alcohol  (95  per  cent.)  and  ether  for  the  same  length  of  time.  Put 
into  thin  celloidin  (5  per  cent,  solution  of  celloidin  in  equal  parts  alcohol  and  ether)  for  sev- 
eral days.  Then  put  into  thick  celloidin  (10  per  cent,  celloidin  in  equal  parts  alcohol  and 
ether)  for  24  hours  or  longer.  The  time  objects  should  remain  in  the  different  solutions 


634  APPENDIX. 

should  be  governed  by  their  size  and  the  character  of  the  tissue.  When  infiltration  is  com- 
plete, place  the  specimen  with  a  considerable  amount  of  the  thick  celloidin  on  a  block  of  wood 
or  of  vulcanized  fiber,  allow  to  stand  in  the  air  until  a  firm  skin  forms,  and  then  immerse 
in  80  per  cent,  alcohol.  This  hardens  the  celloidin  in  several  hours  and  attaches  the  speci- 
men firmly  to  the  block.  The  celloidin  may  be  hardened  and  the  specimen  fixed  to  the 
block  more  quickly  by  immersing  in  chloroform.  The  specimen  is  then  ready  for  cutting. 
Blocked  objects  may  remain  in  the  alcohol  several  months.  A  better  fluid,  however,  is  strong 
alcohol  and  glycerin  in  equal  parts;  in  this  the  celloidin  does  not  become  soft,  as  it  does  after 
several  months  in  plain  alcohol. 

Paraffin  embedding.  Paraffin  with  a  melting  point  of  50°  to  55°  C.  should  be  used,  and 
the  paraffin  oven  kept  at  a  temperature  of  about  56°  C.  The  hardened  tissue  is  placed  in  95 
per  cent,  alcohol  for  several  hours  and  then  in  absolute  alcohol  for  the  same  time.  It  is 
next  transferred  to  oil  of  cedarwood  for  24  hours  (or  xylol  for  6  hours,  or  chloroform  for  6 
hours),  then  into  melted  paraffin  in  the  oven  for  from  i  to  6  hours,  depending  upon  the  size 
of  the  specimen.  The  paraffin  should  be  changed  twice.  Make  a  paper  box  that  will 
considerably  more  than  contain  the  specimen,  fill  the  box  with  melted  paraffin,  and  drop  the 
specimen  into  it.  When  the  paraffin  has  become  cool,  so  that  a  skin  forms  on  the  surface,  put 
it  in  cold  water  (ice-water  if  available)  until  the  paraffin  is  hard.  These  blocked  specimens 
can  be  kept  in  the  air  indefinitely.  For  section  cutting  the  block  is  attached  to  the  metallic 
block-holder  by  heating  the  latter  and  pressing  the  paraffin  down  upon  it. 

VI.  SECTION  CUTTING. 

In  cutting  celloidin  sections  the  microtome  knife  is  adjusted  so  that  it  passes  obliquely 
through  the  specimen  and  must  be  kept  flooded  with  80  per  cent,  alcohol.  The  sections  are 
removed  from  the  knife  with  a  camel's-hair  brush  and  placed  in  80  per  cent,  alcohol  where 
they  may  remain  several  weeks  if  desired.  Equal  parts  strong  alcohol  and  glycerin  will 
preserve  the  sections  indefinitely. 

Celloidin  sections  are  usually  not  cut  thinner  than  8  or  10  microns.  When  thinner 
sections  are  desired,  or  when  large  or  brittle  specimens  are  being  cut,  it  is  often  advantageous 
to  paint  the  surface  of  the  block,  after  cutting  each  section,  with  a  coat  of  very  thin  celloidin. 
The  surface  of  the  block  should  be  dry  before  applying  the  celloidin. 

In  cutting  paraffin  sections,  the  block  containing  the  specimen  is  attached  to  the  block- 
holder,  with  proper  orientation,  and  then  trimmed  so  that  opposite  surfaces  are  parallel. 
The  knife  should  be  used  dry  and  is  passed  straight  through  the  specimen.  The  sections 
are  removed  with  a  camel's-hair  brush  and  laid  upon  a  sheet  of  paper,  where  they  may  be 
kept  for  several  days  at  room  temperature.  They  must  be  kept  in  some  protected  place, 
for  a  slight  draft  will  blow  them  away.  Paraffin  sections  can  usually  be  cut  thinner  than 
celloidin;  under  favorable  circumstances  they  can  be  cut  even  2  or  3  microns  in  thickness. 

Serial  sections  undoubtedly  cut  to  best  advantage  in  paraffin.  Sections  of  embryos  up  to 
10  or  12  mm.  should  be  cut  10  microns  thick;  sections  of  larger  embryos,  15  or  20  microns 
thick.  The  edges  of  successive  sections  adhere,  and  with  care  long  "ribbons"  can  be  ob- 
tained. These  are  arranged  in  order  on  a  piece  of  paper,  and  afterward  mounted  in  order. 
If  the  edges  of  the  sections  do  not  adhere,  or  if  the  sections  curl,  it  usually  means  that  the 
paraffin  is  too  cold,  or  that  the  room  temperature  is  too  low,  or  both.  This  trouble  can  some- 
times be  avoided  by  dipping  the  block  in  melted  paraffin  of  a  lower  melting  point,  or  by 
keeping  a  gas  flame  near  the  microtome.  If  many  sections  are  to  be  cut,  however,  a  room 
temperature  of  70°  to  73°  F.  will  be  found  more  satisfactory. 

Care  should  be  taken  -to  properly  orient  embryos  that  are  to  be  cut  serially.     As  a  rule. 


APPENDIX.  635 

transverse  sections  are  desired,  and  cutting  should  begin  at  the  head  end.  The  dorsal  side 
of  the  embryo  should  be  turned  toward  the  operator.  The  sections  will  then  lie  cranial 
surface  up,  with  the  ventral  side  of  the  embryo  away  from  the  operator.  Sections  mounted 
on  the  slide  in  the  same  relative  position  will  thus  be  seen  right  side  up,  so  to  speak,  under 
the  microscope. 

It  is  always  best  to  mount  paraffin  sections,  especially  serial  sections,  on  the  slide  without 
delay.  This  is  done  as  follows:  Smear  a  very  thin  coat  of  egg  albumen*  on  a  slide  with  the 
finger.  The  slide  must  be  dean.  Put  several  drops  of  distilled  water  on  the  slide,  and 
then  lay  the  sections  on  the  water.  Warm  the  slide  until  the  sections  become  perfectly 
flat,  but  not  enough  to  melt  the  paraffin.  Drain  off  the  excess  of  water  and  put  the  slide  in 
a  dry  place  for  several  hours  until  all  the  water  evaporates.  The  sections  are  then  ready 
for  further  treatment  (see  "Staining  paraffin  sections  with  hasmatoxylin  and  eosin'') 

VII.  STAINING. 

Although  it  is  usually  advisable  to  stain  embryological  material  differentially — a  method 
best  applied  to  sections — it  is  often  convenient  and  saves  time  to  stain  in  toto.  Alum-carmine 
and  borax-carmine  are  two  of  the  most  generally  used  bulk  stains. 

Alum-carmine. — Mix  i  gram  best  carmine  with  100  c.c.  of  a  4  per  cent,  aqueous  solution 
ammonia  (common)  alum.  Boil  15  minutes,  then  add  enough  sterile  water  to  replace  that 
lost  by  evaporation.  When  cool,  filter. 

Small  embryos,  after  being  fixed  and  hardened,  are  placed  in  the  stain  for  24  hours,  then 
washed  in  water,  dehydrated,  embedded,  and  cut  in  the  usual  way. 

Borax-carmine. — Mix  3  grams  best  carmine  and  2  grams  borax  with  50  c.c.  of  water. 
Boil  20  minutes.  When  cool  add  enough  water  to  replace  that  lost  by  evaporation.  Then 
add  50  c.c.  of  70  per  cent,  alcohol,  let  stand  24  hours,  and  filter. 

Small  embryos,  after  being  fixed  and  hardened,  are  put  in  the  stain  for  24  hours  or 
longer;  then  placed  in  70  per  cent,  alcohol,  to  every  100  c.c.  of  which  4  or  5  drops  of  hydro- 
chloric acid  have  been  added,  until  the  specimen  appears  rather  transparent  (several  hours). 
Wash  in  2  or  3  changes  of  70  per  cent,  alcohol,  dehydrate,  embed  and  cut 

DIFFERENTIAL  STAINING  is  most  satisfactorily  done  with  one  of  the  haematoxylin  solutions 
followed  by  a  plasma  stain,  such  as  eosin  or  acid  fuchsin,  or  a  combination  of  picric  acid  and 
fuchsin.     The  following  give  good  results: 
Delafield's  hamaloxylin. — 

Haematoxylin  crystals       i  gm. 

Alcohol       6  c.c. 

Ammonia  alum,  saturated  aqueous  solution, 100  c.c. 

Dissolve  the  hasmatoxylin  in  the  alcohol,  then  add  the  alum  solution.  Allow  the  mixture 
to  stand  in  the  light  for  10  days  to  ripen.  Filter,  and  add  to  the  filtrate  25  c.c.  of  glycerin 
and  25  c.c.  of  wood  naptha.  Allow  to  stand  3  or  4  days  and  filter  again.  It  may  be  used 
in  full  strength  or  diluted  with  water  to  any  degree  desired.  For  using,  see  "Staining  with 
hasmatoxylin  and  eosin." 

Weigerfs  hcemaloxylin. — Make  up  two  stock  solutions  as  follows: 
A.  i  per  cent,  haematoxylin  in  95  per  cent,  alcohol. 

B    Hydrochloric  acid  (sp.  gr.  1.126) 10  c.c. 

Ferric  chloride,  30  per  cent,  solution 40  c.c. 

Distilled  water 95°  c-c- 

*Formula:  Beat  slightly  the  white  of  one  fresh  egg,  filter  (it  will  take  24  hours),  and  add  an 
equal  amount  of  glycerin  and  one  gram  of  salicylate  of  soda.  This  will  keep  for  many  months. 


636  APPENDIX. 

For  use,  mix  equal  parts  of  A  and  B.     The  mixture  will  keep  2  or  3  days.     See  "Staining 
with  haematoxylin  and  eosin." 

Heidenhain's  hcematoxylin. — Make  up  stock  solutions  as  follows: 

A.  Haematoxylin,  i  per  cent,  solution  in  distilled  water. 

B.  Ammonium  sulphate  of  iron,  2.5  per  cent,  aqueous  solution. 
For  using,  see  "Staining  with  Heidenhain's  haematoxylin." 

Eosin. — Dissolve  water-soluble  eosin  to  saturation  in  water.  Precipitate  with  hydro- 
chloric acid  and  wash  with  water  until  the  filtrate  is  tinged  with  eosin.  Dry  the  precipitate 
and  dissolve  in  95  per  cent,  alcohol  in  the  proportion  of  i  gram  to  1500  c.c.  of  alcohol. 

Acid  juchsin  (FuchsinS,  Rubin  S}. — This  is  generally  used  in  a  0.5  per  cent,  solution  in 
distilled  water.  It  is  very  sensitive  to  alkalies  and  to  avoid  washing  out  the  stain,  distilled 
water  should  be  used  for  washing  the  sections.  The  dye  known  as  Orange  G  is  used  in  the 
same  solution  and  with  the  same  precautions  (see  also  p.  290). 

Picric  acid  and  acidfuchsin  (Picro-acid  fuchsin) . — 

Acid  fuchsin,  i  per  cent,  aqueous  solution 5  c.c. 

Picric  acid,  saturated  aqueous  solution 100  c.c. 

For  using,  see  under  "Staining  with  haematoxylin  and  eosin."     The  proportions  may  be 
varied  if  desired. 

Staining  celloidin  sections  with  hcemaloxylin  and  eosin. — Starting  with  sections  in  80  per 
cent,  alcohol,  transfer  to — 

1.  Water. 

2.  Delafield's  or  Weigert's  haematoxylin,  several  minutes. 

3.  Water  (to  wash).. 

4.  Water  acidulated  with  HC1  (6  drops  of  HC1  to  50  c.c.  of  water)  until  tissues  appear 
gray. 

5.  Water  made  slightly  alkaline  with  ammonia. 

6.  Water,  several  changes. 

7.  Alcohol,  80  per  cent. 

8.  Eosin  solution  until  tissues  are  pink. 

9.  Alcohol,  95  per  cent. 

10.  Carbol-xylol  (carbolic  acid,  i  vol.;  xylol,  3  vols.). 

11.  Pure  xylol  (one  change). 

12.  Mount  in  xylol-damar. 

If  many  sections  are  to  be  stained  it  is  most  convenient  to  carry  them  through  the  various 
fluids  up  to  95  per  cent,  alcohol  in  small  sieves  or  perforated  porcelain  dishes  and  then 
transfer  them  one  by  one  to  the  carbol-xylol. 

If  acid  fuchsin,  instead  of  eosin,  is  to  be  used  as  a  counter -stain,  carry  the  sections  through 
the  various  fluids  up  to  and  including  (6).  Then  immerse  in  the  fuchsin  solution  until  the 
tissues  are  pink  (several  seconds  to  several  minutes),  wash  in  distilled  water  and  continue  the 
steps  as  given,  omitting  of  course  the  eosin  solution. 

The  picric  acid  and  acid  fuchsin  mixture  is  used  in  exactly  the  same  way  as  the  fuchsin. 

Staining  paraffin  sections  with  hcematoxylin  and  eosin.- — It  is  most  convenient  to  have  the 
fluids  in  Coplin  jars.  Starting  with  sections  on  slides  from  which  the  paraffin  has  not  been 
dissolved,  transfer  to — 

1.  Xylol,  two  successive  baths. 

2.  Absolute  alcohol,  two  successive  baths. 

3.  Alcohol,  95  per  cent. 

4.  Alcohol,  80  per  cent. 

5.  Water. 


APPENDIX.  637 

6.  Delafield's  or  Weigert's  haematoxylin,  several  minutes. 

7.  Water  (to  wash). 

8.  Water  acidulated  with  HC1  (6  drops  HC1  to  50  c.c.  water)   until  tissues  appear  gray. 

9.  Water  made  slightly  alkaline  with  ammonia. 

10.  Water,  several  changes. 

11.  Alcohol,  80  per  cent. 

12.  Eosin  solution  until  tissues  are  pink. 

13.  Alcohol,  95  per  cent. 

14.  Absolute  alcohol,  or  carbol-xylol. 

15.  Xylol,  two  successive  baths. 

16.  Mount  in  xylol-damar. 

Staining  with  Heidenhain's  hcematoxylin. — This  can  be  done  with  either  paraffin  or  celloi- 
din  sections.  The  following  is  the  method  pursued  for  paraffin  sections.  Starting  with 
sections  mounted  on  slides  from  which  the  paraffin  has  not  been  dissolved,  transfer  to — 

i,  2,  3,  4,  5,  as  given  in  the  preceding  table. 

6.  Ammonium  sulphate  of  iron,  2.5  per  cent,  aqueous  solution,  12  to  24  hours. 

7.  Water  (to  wash). 

8.  Haematoxylin,  i  per  cent,  solution  (as  stated  on  p.  636),  6  to  12  hours. 

9.  Water  (to  wash). 

10.  Ammonium  sulphate  of  iron  (as  above)  until  tissues  appear  gray.     It  is  best  to 
examine  the  tissues  under  the  microscope  from  time  to  time. 

11.  Water,  several  changes. 

12.  Alcohol,  80  per  cent. 

13.  Alcohol,  95  per  cent. 

14.  Absolute  alcohol  or  carbol-xylol. 

15.  Xylol,  two  successive  baths. 

16.  Mount  in  xylol-damar. 

VIII.  METHODS  OF  RECONSTRUCTION. 

Graphic  reconstructions. — Making  reconstructions  of  this  kind  consists  o"  plotting  out  on 
paper  magnified  representations  of  structures  from  a  series  of  sections.  Serial  sections  are 
of  course  necessary,  and  the  thickness  of  the  sections  must  be  known.  A  camera  lucida  must 
be  used  and  some  given  magnification  chosen  and  adhered  to  for  a  particular  reconstruction. 

Suppose,  for  a  simple  example,  that  a  reconstruction  of  the  stomach  of  an  embryo  is  to 
be  made.  First  determine  the  desired  magnification.  Then,  with  a  camera  lucida,  draw  on 
a  sheet  of  paper  an  outline  of  a  section  of  the  stomach  at  its  cephalic  end,  and,  still  keeping 
the  paper  in  exactly  the  same  position,  draw  a  line  to  represent  the  median  line  of  the  section. 
On  a  sheet  of  drawing  paper,  upon  which  a  straight  line  has  been  drawn  to  represent  the 
median  line  of  the  section  (sagittal  plane  of  the  embryo),  measure  off  the  distance,  as  indicated 
in  the  camera  lucida  sketch,  of  each  edge  of  the  stomach  from  the  median  line  and  mark 
with  a  dot. 

Make  the  same  kind  of  a  camera  lucida  sketch  from  the  next  succeeding  section.  Plot 
this  on  the  drawing  paper  as  in  the  preceding  case,  putting  the  dots  below,  or,  so  to  speak, 
caudal  to  the  first  dots  at  a  distance  equal  to  the  thickness  of  the  section  multiplied  by  the 
magnification. 

Pursue  the  same  method  with  successive  sections,  and  then  connect  the  dots  that  rep- 
resent the  edge  of  the  stomach  in  the  sections  with  a  continuous  line.  The  line,  of  course, 
represents  the  outline  of  the  stomach,  and,  if  the  plotting  has  been  properly  done,  it  will 


638  APPENDIX. 

show  the  relative  position  and  general  shape  of  the  organ  as  seen  from  the  dorsal  or  ventral 
side.     If  desired,  the  sketch  can  be  shaded  to  represent  the  stomach  in  perspective. 

Drawings  of  two  or  three  different  structures  to  show  their  interrelation  can  be  made 
in  this  way,  so  long  as  the  structures  do  not  become  too  complicated.  Sometimes  it  is  neces- 
sary to  draw  only  from  every  third  or  fourth  section. 

Plastic  or  Wax  Reconstructions. — These  are  simply  wax  models  of  an  organ  or  a  system, 
and  are  built  up  from  pieces  of  wax  which  represent  magnified  sections  of  the  embryonic 
structures.  Here,  as  in  the  case  of  graphic  reconstructions,  serial  sections  of  a  known 
thickness  are  necessary.  A  camera  lucida  also  is  necessary.  Wax  plates  for  this  work  can 
be  purchased  from  firms  that  trade  in  scientific  apparatus.  Plates  i  mm.  or  2  mm.  in  thick- 
ness are  most  convenient,  for  they  must  represent  a  definite  magnification  of  the  thickness  of 
the  sections  from  which  the  reconstruction  is  to  be  made.  For  example,  if  the  magnifica- 
tion is  50  times  and  the  sections  20  microns  thick,  the  plates  should  be  50  times  20  microns, 
i.e.,  one  millimeter  in  thickness. 

As  a  simple  example  of  this  kind  of  reconstruction,  suppose  a  model  of  the  embryonic 
liver  is  to  be  made,  the  sections  being  20  microns  thick  and  50  the  chosen  magnification. 
Select  the  section  containing  the  cephalic  edge  of  the  liver  and  with  the  camera  lucida  trace 
the  outline  of  the  organ  and  the  median  line  of  the  section  on  one  of  the  wax  plates.  The 
plate  should  be  i  mm.  in  thickness  because  that  represents  the  thickness  of  the  section 
magnified  50  times.  Lay  the  plate  upon  a  smooth  hard  surface  and,  with  a  thin-bladcd 
knife,  cut  out  ihe  piece  indicated  by  the  outline  tracing  of  the  liver. 

Do  exactly  the  same  with  successive  sections,  keeping  the  corresponding  pieces  of  wax 
in  order.  Then  arrange  the  pieces  of  wax,  that  is  pile  them  up,  in  the  same  order,  being 
careful  that  the  lines  traced  upon  them  to  represent  the  median  lines  of  the  sections  come  in 
the  same  plane.  (This  plane  represents  the  median  sagittal  plane  of  the  embryo.)  When 
properly  piled,  the  wax  plates  form  a  mass  which  represents  the  embryonic  liver  magnified 
50  times.  The  plates  are  fastened  together  by  passing  a  warm  metal  instrument  over  their 
edges,  thus  slightly  melting  the  wax. 

By  the  same  method,  whole  systems  o.  organs  or  even  whole  embryos  can  be  reconstructed. 
With  complicated  structures,  however,  the  utmost  care  is  required  to  place  the  various  parts 
in  their  proper  relative  positions. 

In  case  of  structures  consisting  of  many  parts,  like  the  vascuiar  system,  lor  example,  it  is 
scarcely  possible  to  trace  and  cut  out  the  various  pieces  of  wax  and  put  them  together  again 
without  fastening  together  each  time  the  parts  that  belong  to  each  section.  The  best  method 
to  follow  in  such  cases  is  as  follows:  Make  the  camera  lucida  sketch,  including  the  median 
line,  of  each  section  on  a  sheet  of  paper.  By  means  of  carbon  paper  transfer  the  tracings  of 
the  various  parts  to  the  wax.  Cut  out  the  pieces  of  wax  and  lay  them  in  their  proper  posi- 
tions on  the  sheet  of  paper.  Then  fasten  them  all  together  by  means  of  pieces  of  fine  copper 
wire  heated  to  such  a  temperature  that  when  laid  upon  the  vax  they  will  sink  into  it.  If  this 
is  done  with  the  pieces  belonging  tc  each  section,  then  the  pieces  belonging  to  successive 
sections  can  be  piled  and  fastened  together  by  passing  a  warm  metal  instrument  over  their 
edges. 

References. 

LEE,  A.  B.:  "The  Microtomist's  Vade-Mecum."  Sixth  Edition.  P.  Blakiston's  Son 
&  Co.  Philadelphia,  1905. 

MALLORY,  F.  B.,  and  WRIGHT,  J.  II.:  "Pathological  Technique."  Third  Edition.  Saun- 
ders  &  Co.  Philadelphia,  1908. 

MINOT,  C.  S.:  "A  Laboratory  Text-book  of  Embryology."  P.  Blakiston's  Son  & 
Co.  Philadelphia,  1903. 


INDEX. 


Abdominal  cavity,  340,  379 

regions,defects  of,  622 
Abducens,  VI,  nerve,  469,  471 
Aberrant  ductule,  421 
Abnormal  embryos,  1 58 
Abrachius,  623 
Acardia,  285,  607 
Acardiaci,  acephali,  608 

acormi,  608 

amorphi,  608 

completi,  608 
Acardiacus,  607 

Accessory  chromosomes,  28,  416 
Achromatic  spindle,  4 
Acid  fuchsin,  636 
Acini,  the,  450 
Acoustic  area,  (see  also  Auditory  area),  565 

ganglion,  598 

VIII,  nerve,  469,  472,  506,  507,  510, 

S25,  598 

nerve,  ganglion  cells  of,  599 

radiation,  477,  478 
Acrania,  616,  617,  619 

with  exencephaly,  617 
Acrocephaly,  216 
Acromion  process,  203 
Acrosome,  14 

Acustico-facialis  ganglion,  598 
Acustico-lateral  system, 

influence    on    nervous    system,    459, 

466,  473 

Adami,  concerning  hermaphroditism,  439 
Adenoid  tissue,  332 
Adipose  tissue,  171 
Aditus  laryngis,  362,  363 
After-brain  (myelencephalon) ,  462 
After-birth,  134 
Afferent  root  fibres,  458 
Afferent   peripheral    neurones,  454,     464, 
_  496  to  509. 

peripheral  nerve  fibres,  458 
Agnathus,  357,  621 
Ahlfeld's    fission    theory    of    symmetrical 

duplicity,  6n 
Air  sacs,  367 
Ala  cinerea,  531 

magna,  195 

parva,  195 
Alar  plate,  484,  497,   519,   522,   526,   530, 

Albinism,  452 

Albrecht,  concerning  formation  of  incisive 

bone,  200 

Alcohol,  for  fixation,  631 
Alecithal  ova,  42,  43 

(mammalian),  method  for  study  of,  1 5 


Alimentary  tube,  317 

intestinal  region  of,  318 

oesophageal  region  of,  318 

origin  of,  317,  318 

pharyngeal  region  of,  318 

stomach  region  of,  318 

yolk  stalk  of,  318 
Alimentary   tube   and   appended   organs, 

3  7        * 
anomalies  of,  ?  c  « 

.  t        '     \J  *J  u 

histogenesis  of  gastrointestinal  tract, 

,343 

of  liver,  3  50 
of  pancreas,  3  54 

intestine,  338 

liver,  346  . 

mouth,  318 

oesophagus,  336 

pancreas,  351 

pharynx,  330 

practical  suggestions  for  study  of,  359 

salivary  glands,  328 

stomach,  336 

teeth,  323 

tongue,  321 
Alisphenoid  bone,  195 
Allanto-chorion,  106 
Allantoic  blood-vessels,  in  Mammals,  108 

duct,  1 18,  338 

sac,  1 08 
Allantois,  the,  106 

blood-vessels  of,  in  chick,  107 
in  Mammals,  113 
in  man,  119 

functions  of,  in  chick,  106 
in  man,  1 18 

in  Mammals,  1 1 1 
.in  man,  118 

relation  of,  to  chorion,  106 
Allen,  concerning  sex  cells,  407 
Alopecia,  452 
Alternation   of  vertebrae   and  myotomes, 

184,  295 

Alum-carmine,  635 
Amelus,  623 
Amitosis,  3 

diagram  showing,  4 

Amnion,   formation    from   amniotic  fold, 
101 

in  Birds,  99 

in  Mammals,  108,  no 

in  man,  115 

in  Reptiles,  99 

practical  suggestions  for  study  of,  135 

rhythmical  contractions  of,  102,  116 

false,  102 


639 


640 


INDEX. 


Amniotic  adhesions,  623 

cavity,  68,  101,  115,  137 

fluid,  116 

folds,  100 

in  Mammals,  no 

suture,  100 

Amoeboid  movement  of  nuclei,  2 
Amphiaster,  4 

Amphibian  embryos,  technic  for,  629 
Amphibians,  cleavage  in,  44 

gastrulation  in,  56 

mesoderm  formation  in,  76 
Amphicytes,  499 
Amphioxus,  cleavage  in,  43 

gastrulation  in,  55 

germ  layers  of,  7  5 

mesoderm  formation  in,  72 
Ampullae  of  semicircular  canal,  593,  598 
Amyelus,  618 
Anal  membrane,  342 

opening,  342 

pit,  342 
Anaphase,  6 
Anencephaly,  313,  620 
Angiomata,  452 

Angle  of  the  mouth,  145,  152,  319 
Angulus  praethalamicus,  541,  547,  554 
Ankyloblepharon,  620 
Animal  pole  (micromere),  56 
Animalculists,  XIII 
Annular  placenta,  134 
Anophthalmia,  620 
Anomalies,  (see  also  Terato gene sis) 

of  the  alimentary  tract,  355 

of  the  diaphragm,  384 

of  the  large  vascular  trunks,  286 

of  the  heart,  285 

of  the  integumentary  system,  451 

of  the  mesenteries,  384 

of  the  muscular  system,  313 

of  the  nervous  system,  567 

of  the  omenta,  384 

of  the  placenta,  134 

of  the  pericardium,  384 

of  the  respiratory  system,  366 

of  the  skeletal  system,  213 

of  the  umbilical  cord,  135 

of  the  vascular  system,  285 

of  the  urogenital  system,  433 
Anomalous  position  of  the  heart,  285 
Anterior    colliculi,    see    Anterior    corpora 

quadrigemina 
Anterior  (cerebral)  commissure,  461 

commissure  of  the  cord,  510,  514 

corpora  quadrigemina,  474,   524,  537, 
540,  586 

horn  (ventral  gray  column),  514 

neuropore,  458 

perforated  space,  548 
Antitragus,  60 1 
Anthelix,  60 1 
Aortic  arches,  231,  239 
Aorta,  dorsal,  239 
Aortas,  primitive,  239 

Apathy,  concerning  peripheral  nerves,  501 
Apical  body,  14 
Apolar  cells,  491 


Appendage  of  the  epididymis,  420 
Appendicular  skeleton,  202 

anomalies  of,  216 

derivation  of,  203 

practical  suggestions  for  further  study 

of,  219 
Appendix,  629 

testis,  421 

vermiform,  342 
Aprosopus,  620 
Apus,  623 

Aquasductus  Sylvii,  463 
Arch  of  the  aorta,  245 
Archencephalon,  460 
Archenteron,  55,  60 

of  Amphibians,  57 

of  Amphioxus,  55 

of  Birds,  67 

of  Reptiles,  64 

Archipallial  commissure,  see  Fornix  com- 
missure 
Archipallium,  475,   512,    544,   548,    553  to 

559 

connections  of,  512,  544,  565 
Arcuate  fibers  (external),  522 

(internal),  515,  522 
Arcus  aortae,  245 
Area  opaca,  65 

pellucida,  65,  83 

of  supplemental  cleavage,  64 
Areolar  tissue,  170, 

origin  of  fibers  of,  171 
Areola,  the,  450 
Area  vasculosa,  83,  105,  273 
Arm,  development  of,  i  54 
Arrectores  pilorum,  445 
Arteria  centralis  retinae,  579 

intercostalis  suprema,  248 
Arteries,  243 

allantoic,  243 

anomalies  of,  286 

basilar,  246 

brachial,  252 

carotid,  244 

cerebral,  247 

cceliac,  249 

epigastric,  248 

femoral,  252 

gastric,  249 

gluteal,  253 

hepatic,  249 

hyaloid,  579 

hypogastric,  2  50 

iliac,  250 

innominate,  245 

intercostal,  248 

lumbar,  248 

mammary,  248 

median,  251 

mesenteric,  248 

omphalomesenteric,  105,  107,  239 

ovarian,  250 

peroneal,  2  53 

popliteal,  253 

pulmonary,  231,  246 

radial,  252 

renal,  249 


INDEX. 


641 


Arteries,  saphenous,  252 
sciatic,  252 
spermatic,  249 
splenic,  249 
subclavian,  245 
testicular,  250 
tibial,  252,  253 
ulnar,  251 
umbilical,  107,  243 
vertebral,  246 
vesical,  2  50 
volar  interosseous,  251 
vitelline,  105,  107,  239 
Articular  cavity,  210 
Aryepiglottic  ridges,  363 
Arytenoid  ridge,  363 

Ascaris  megalocephala,  for  study  of  matu- 
ration, 33 
Assheton,    concerning   origin  of  parasitic 

duplicity,  615 
Aster,  2,  3,  7 
Astomus,  621 
Astragalus,  the,  208 
Asymmetrical  duplicity,  612 
origin  of,  614 
parasitic    structures    in    the    sexual 

glands,  613 
Atlas,  the,  188 
Atresia  of  the  anus,  3  58 

oris,  62 1 

Atria  of  lungs,  367 
Atrial  septum,  228 
Atrio- ventricular  canal,  228 
Atrium  of  inner  ear,  593 
Attraction  cone,  38 
sphere,  2,  3,  4 

Auditory  area  of  pallium,  477,  564,  565 
meatus,  external,  origin  of,  147,  151, 

601 

nerve,  see  Acoustic  VIII 
ossicles  derivation  of,  201,  599 
pit,  592 
placode,  592 
vesicle,  592 

Auerbach,  plexus  of,  498 
Aula,  549 
Auricle,  600 

Autonomic  system  (sympathetic),  465 
Autosite,  610 
Axial  filament,  14 
skeleton,  182 

anomalies  of,  213 

head,  190 

notochord,  182 

practical    suggestions    for    further 

study  of,  218 
primitive,  182 
ribs,  1 88 
sternum,  189 
vertebrae,  183 
thread,  14 

Axis  (epistropheus),  188 
Axone,  the,  485,  492 

Balfour,  concerning  peripheral  nerves,  500 
Bardeen,  concerning  peripheral  nerves,  500 
Bartholin's  glands,  406 


Basal  plate,    129,  484,  509,  514,  519,  521, 

S31 

Basilar  artery,  246 
Basioccipital  bone,  194 
Basisphenoid  bone,  195 
Baskets,  536 
Basket  cells,  536 
Belly  stalk,  96,  118,  140 
Beard,  concerning  sex  cells,  407 
Bechterew,  v.,  central  tegmental  tract  of, 

526 

Bertini,  columns  of,  400 
Bicornuate  uterus,  437 
Bielschowsky,  method  of  staining,  570 
Bilateral  hermaphroditism,  438 
Bile  capillary,  350 
Biophores,  29 
Bipartite  uterus,  437 
Birds,  cleavage  in,  46 

gastrulation  in,  61 
Bischoff,    concerning    origin    of    parasitic 

duplicity,  615 
Bladder,  (see  also  Urinary  Bladder),  403 

anomalies  of,  435 

practical  suggestions  for  study  of,  440 
Birds,  mesoderm  formation  in,  78 
Blastodermic  vesicle,  138 
Blastema,  metanephric,  395 
Blastema!  stage,  184 
Blastoderm,  50,  61,  63,  137 

method  for  study  of,  97 
Blastomeres,  42 
Blastopore,  55 

Blastopore  (crescentic  groove),  63 
Blastula,  50,  137 
Blood,  cells  of,  270 

practical  suggestions  for  study  of,  289 

relation  of  maternal  and  foetal  blood 
in  Mammals,  113 
in  man,  119,  131 
Biood  cells,  development  of,  270 

erythroblasts,  primitive,  271,  272 

erythrocytes,  272,  274 

erythrocytes,  primitive,  273 

histogenesis  of,  270 

leucocytes,  274,  275 

lymphocytes,  271,  272,  273,  274,  275 

megaloblasts,  272,  273,  274 

mononuclear  leucocytes,  275 

normoblasts,  272,  273,  274 

polymorphonuclear  leucocytes,  275 

polynuclear  leucocytes,  275 

primitive,  271,  273 

relation  to  thymus,  275 
Blood  islands,  237,  271 
Blood  plates,  275,  276 
Blood  vessels,  allantoic,  function  of,   108 

arteries,  243 

growth  of,  237 

heart,  222 

Knower's    method    of  injecting  with 
India  ink,  291 

origin  of,  235,  237 

placental,  131,  243 

practical  suggestions  for  study  of,  289 

segmental  cervical,  246 

sinusoids,  259,  263 

veins,  253 


642 


INDEX. 


Blue  babies,  287 

Body  cavity,  see  Coelom 

Boll,  concerning  the  origin  of  connective 

tissue  fibers,  170 
Bone,  compact,  176 

diaphysis  of,  180 

epiphysis,  180 

growth  of,  1 80 

method  for  study  of,  180 

intracartilaginous,  176 
methods  of  study  of,  218 

shaft  of,  1 80 

spongy,  175 

subperiosteal,  176 

transparent    preparations    for    study 

of,  219 
Bone  cells,  175 

destroyers,  175 

formers,  175 

marrow,  181 

haematopoietic  function  of,  272 
Bones,  defective  or  absent,  623 

derived  from  the  branchial  arches,  198 

membrane,  of  the  skull,  196 
Bonnet,  concerning  derivation  of  pigmen- 
ted  layer  of  retina,  587 

concerning  double  origin  of  vitreous, 

585 
concerning  the  Erganzungshohle,    59, 

60 

concerning  the  Erganzungsplatte,  60 
concerning  origin  of  parasitic  duplic- 
ity, 615 
concerning    the    primitive    intestinal 

cord,  66 

concerning   the   primitive   streak,    65 
concerning  gastrulation,  55 
Borax-carmine,  63  5 
Born,  concerning     potentiality    of     germ 

cells,  616 
Bouin's  fluid,  631 
Boveri,  concerning  the  "dynamic  center" 

of  the  cell,  8 

Bowman's  capsule,  390,  398 
Bowman,  membrane  of,  588 
Brachia,  anterior,  537,  540 
Brain,  the,  460,  480 

after-brain  (myelencephalon),  462 
aquaeductus  Sylvii,  463 
archencephalon,  460 
cephalic  flexure  of,  461 
cerebellum,  462,  484,  519,  532 
corpora    striata,    462,  474,  481,  485, 

546,  548 

defects  in,  616,  617 
deuterencephalon,  460 
diencephalon,  462,  474,  481,  485,  538 
distinguishing  features  of  human  and 
their  biological  significance,  475, 

477 

end-brain  (telencephalon),  462 
epichordal  part  of,  460,  464 
epichordal  segmental,  519 
fore-brain  (prosencephalon),  461 
hind-brain  (metencephalon),  462 
inter-brain  (diencephalon),  462 
isthmus,  462,  520 


Brain,  medulla  oblongata,  484,  519 

mid-brain  (mesencephalon),  461 

plica  encephali  ventralis,  460 

plica  rhombo-meseucephalica,  482 

prechordal  part,  460,  464 

rhinencephalon,  462,  474,  512,  544, 
547  to  548 

rhombic  (rhombencephalon),  461 

rhombo-mesenceph'ilic  fold  of,  461 

segmental,  464 

segmental  character  of,  463,  464 

telencephalon,  462,  474,  545  to  568 

ventral  cephalic  fold,  460 

ventricles  of,  463,  485,  549 
Branchial  arches,  malformations  of,  620 

arches,  origin  of,  144,  150 

cysts,  622 

epithelial  bodies,  332 
glomus  caroticum,  336 
parathyreoids,  333 
thymus,  334 
thyreoid  gland,  332 

grooves,  origin  of,  144,  150 
Branchiogenetic  cysts,  622 
Branchiomeric  muscles,  302 

segmentation,  467,  496 

Brachium     conjunctivum,     see     Superior 
cerebellar  peduncle 

pontis,  see  Middle  cerSbellar  peduncle 

quadrigeminum  inferius,  478 
Brandt      concerning    anomalies    of    hair, 

452 
Bremer,  concerning  spinal  acessory  nerve, 

5°3 

Brodmann,  concerning  cortical  layers,  563 
Bronchial  rami,  366 

Brooks   and  Weisman,  concerning  fertili- 
zation, 40 

Brunner,  glands  of,  344 
Bryce-Teacher's  ovum,  90,  94,  96,  115,  121 
Bucco-nasal  membrane,  590 
Burdach,  columns  of,  466,  478,  525 

nuclei  of  the  columns  of,   466,  473, 

474,  527 
Bursa  pharyngea,  332 

Caecum,  the,  338,  341 

Cajal,    concerning    development    of    cere- 
bellar cells,  53  5 

concerning  neurofibrils  and  early 
development  of  nerve  cells,  491, 
492 

concerning  optic  nerve,  586    , 

concerning  peripheral  nerves,  501 

methods  of  staining,  569 
Calcaneus  (os  calcis),  208 
Calcar  avis,  560 
Calcarine  area,  477 
Calcification  centers,  173,  177 
Calcification  zone,  176,  178 
Calyces,  396 

Campbell,  concerning  cortical  areas,  566 
Canal  of  Cloquet,  586 
Canal  of  Petit,  588 
Canalized  fibrin,  126 
Canals  of  Gartner,  420 
Capillaries,  villous,  131 


INDEX. 


643 


Capitulum  of  rib,  189 
Capsule  of  Glisson,  347,  376 
Carney's  fluid,  632 
Carotid  arteries,  244 

gland,  433 

skein,  433 
Carpal  bones,  204 

Carpenter,  concerning  ciliary  ganglia,  508 
Cartilage,  172 

cuboid,  208 

cuneiform,  208 

episternal,  189 

ethmoidal,  196 

laryngeal,  364 

Meckel's,  193,  198 

of  hip  bone,  207 

thyreoid,  364 

triticeous,  364 

Wrisberg's,  365 
Cartilaginous  primordial  cranium,   192 

stage,  184 
Cauda  equina.  519 
Caudal  gut,  343 

lymph  sac,  277,  278 
"Caul,"  117 
Cavity,  abdominal,  379 

amniotic,  68 

body,  372 

completion,  59,  60,  63 

extraembryonic  body,  96,  372 

invagination,  63 

parietal,  222,  373 

pericardial,  372,  373 

peritoneal,  372,  375 

pleural,  372,  375 

primitive  pericardial,  88,  222,  373 

segmentation,  50,  58,  63 
Cell,  the  typical  animal,  i 

centrosome  of,  i 

diagram  of,  2 

functions  of,  2 

nucleus  of,  i 

structure  of,  i 
Cell  division,  3 

direct  or  amitosis,  3 

indirect,  or  mitosis,  4 

practical  suggestions  for  study  of,  9 

references  for  further  study  of,  9 
Cell   migration,    of   nervous   system,   485, 

486,  491,  492,  493,  526,  534 
Cell-plate,  8 
Cell  proliferation,  486,  521,  526,  534 

in  neural  tube,  486 
Celloidin  embedding,  633 

sections,  staining  with    haematoxylin 

and  eosin,  636 
Cells,  air,  367 

apolar  of  neural  tube,  491 

association,  464,  475,  535,  537,  565 

basket,  536 

bipolar  of  neural  tube,  491 
of  retina,  583 

blood,  270 

bone,  175,  178 

chromamn,  430 

cochlear  ganglion,  599 

cone,  508,  512,  582,  583 

daughter,  3 


Cells,  decidual,  127 

dermal,  449 

ependyma,  488,  490 

epithelial,  486 

fat,  172 

follicular,  411 

germinal  of  neural  tube,  486,  490 

giant,  181 

granddaughter,  28 

granule,  535 

hair,  596,  598,  599 

heart-muscle,  293,  312 

Hensen's,  598 

indifferent,  407 

of  neutral  tube,  491 

interstitial,  415 

liver,  350 

lutein,  32,  413 

lymphoid,  336 

mastoid,  600 

mesodermal,  372,  445 

mitral,  512 

monopolar,  492 

myelocytes,  182 

Muller's,  582 

myoblasts,  307 

neuroglia,  488,  490 

odontoblasts,  326 

osteoblasts,  175^  275 

osteoclasts,  175 

phaeochrome,  430 

pillar,  598 

polymorphous,  564 

Purkinje,  534 

pyramid,  562,  563,  565 

rod,  508,  512,  582,  583 

solitary,  of  Meynert,  565 

spermatids,  21 

of  Sertoli,  21,  415 

sex,  407 

somatic,  75,  416 

spermatogenjc,  21 

spermatocytes,  2 1 

spermatogonia,  21 

supporting,  21.  415, 

sustentacular,  582 

yolk    57 

vestibular  ganglion,  599 

yolk  (or  merocytes),  63 

wandering,  355 

Cement  substance,  origin  of,  169 
Central  canal,  516 
Central  spindle,  4 

fibres  of,  6 
Centralis,  533 

Centriole,  the,  2,  3,  4,  5,  6,  7,  8 
Centrolecithal  ova,  42,  45 
Centrosphere,  the,  3,  4 
Centrosome,  the,  2,  3,  8 
Cephalic  flexure,  143,  461,  480 
Cephalization,  457 
Cephalocele,  617 
Cephalopagus,  610 
Cephalopods,  cleavage  in,  49 
Cephalothoracopagus  diprosopus,  609 

janiceps,  6 to 
Cerebellar  hemispheres,  479,  533 


644 


INDEX. 


Cerebellum,  462,  464,  473,  519,  532 

afferent  connections  of,  473 

basket  cells  of,  536 

cells  of  Purkinje,  534,  536 

centripetal  fibers  of,  536 

climbing  fibers  of,  537 

cortex  of,  534 

efferent  connections  of,  473 

flocculi,  533 

granular  layer  of,  534 

granule  cells  of,  53  5 

hemispheres  of,  479,  533 

lobes  of,  533 

middle  peduncle  of,  473,  479 

molecular  (plexiform)  layer,  534 

mossy  fibers,  537 

nodule,  533 

parallel  fibers  of,  53  5 

peduncles  of,  473,  478,  480,  530,    537 

postnatal  development,  535,  536 

superior  peduncle  of,  473 

tajnia  of,  520 

velum  of,  520 

vermis  of,  533 

Cerebral   hemispheres,    see   also   Pallium, 
464,   477,   48i,    545,    548   to    567 

hernia,  617 

Cerebrospinal  ganglia,  458 
Cervical  depression,  146 

enlargement,  466 

fistulas,  complete,  621 
incomplete,  621 

flexure,  144,  485 
Cervix,  the,  419 

plicae  palmata?  of,  419 
Chalaza,  13 

Cheilognathoprosoposchisis,  621 
Cheilognathoschisis,  621 
Cheilognathouranoschisis,  621 
Cheiloschisis,  621 

Chiari,  concerning    sebaceous    cysts,    452 
Chiasma  eminence,  461 
Chick  embryos,  technic  for,  630 
Chin,  origin  of,  148 
Choanen,  primitive,  590 
Chondrification   first   occurrence   in   head 

skeleton,  192 
Chondrocranium,  193 

ossification  of,  194 
Chorda,  (see  also  Notochord),  72 

anlage,  91 

dorsalis,  182 

tympani,  469,  505 
Chorda?  tendinas,  232 
Chordal  plate,  72 

sheath,  182 

Chorio  epitheliomata,  436 
Chorioid,   defective  pigmentation  of,   452 

fissure,  of  pallium,  554 

fold,  554 

of  rhombencephalon,  520 

of  eye,  585 

plexus  of  fourth  ventricle,   460,  520, 

S32 

of  lateral  ventricle,  460,  540,  550,  554 
of  third  ventricle,  460,  540 
Chorioidal  fissure  of  eye,  577,  585 


Chorion,  in  chick,  107 

in  Mammals,  108,  no 

in  man,  1 19,  139 

practical  method  of  studying,  135 

primitive,  102 
function  of,  107 

relation  of,  to  allantois,  119 
Chorion  frondosum,  122,  124 

practical  suggestions  for  study  of,  135 

lasve,  122,  124 
Chorionic  villi,  114,  122 

in  von  Spec's  embryo,  92 
Chromaffin  cells,  430 

granules,  430 
Chromatin,  i 

Chromophilic  bodies,  485,  496 
Chromosomes,  5,  6,  7 

U  or  V  shaped,  5,  6 

accessory,  28 
Chryptorchism,  436 
Cilia,  of  the  cells  of  gastrula,  55 
Ciliary  body  of  eye,  587 

ganglion,  508 
Circulation,  changes  in,  at  birth,  267 

reversal  of,  607 

vitelline,  239,  242 

fcetal,  course  of,  234 
Circulus  arteriosus,  247 
Cisterna  chyli,  277 
Clark,  W.  C.,  concerning  the  joint  capsule 

and  cavity,  213 
Clarke's  columns,  473,  518 
Clava,  531 
Clavicle,  204 
Cleavage  (segmentation),  42 

bilateral,  49 

determinate,  49 

discoidal,  46 

equal,  43 

forms  of,  42 

general  features  of.  47 

holoblastic,  43,  49 

meroblastic,  45 

in  Amphioxus,  43 

in  Birds,  46 

in  the  frog,  44 

in  Mammals,  47 

in  man,  89 

in  Synapta,  43 

indeterminate,  49 

practical  suggestions  for  study  of,  53 

radial,  49 

spiral  or  oblique,  49 

superficial,  45 

unequal,  44 

Cleft  palate,  216,  620,  621 
Climbing  fibers,  537 
Clitoris,  the,  428 
Cloaca,  the,  342,  403 

persistence  of,  3  58 
Cloacal  membrane,  403 
Closed  skein,  5 
Closing  plate,  129 
Coccygeal  gland,  285 
Cochlea,  467,  474 
Cochlear  ganglion  cells,  599 
Cochlear  ganglion  of  VIII  nerve,  506 


INDEX. 


645 


Cochlear     part     of     acoustic      (auditory) 

nerve,  469 
Cochlear  pouch,  593 
Cochlear  terminal  nuclei,  473 
Ccelenteron,  (see  also  Archenterori),  55 
Ccelom  (myocoel),  74,  372 
embryonic,  372 

practical  suggestions  for  study  of,  385 
Collaterals,  511,  536,  563 
Colloid  secretion  of  thyreoid  gland,  332 
Colon,  the,  339 

ascending,  341 
descending,  341 
sigmoid,  341 
transverse,  341 
Colostrum  corpuscles,  451 
Column  cells,  510 

heteromeric,  510 
tautomeric,  510 
Columns,  anterior  white,  514 

dorsal  gray  (posterior  horn),  465,  515 
posterior  white,  497,  510,  514 
Columns  of  Bertini,  400 
Columns  of  Burdach,  466,  478,  525 

nuclei  of,  466,  478,  527 
Columns  of  Goll,  466,  478,  517,  525 

nuclei  of,  466,  478,  527 
Commissura  habenularis,  462,  545 
Commissural  column  cells,  510 
Commissure,  anterior,  (cerebral),  461 
neopallial,  475 
posterior,  461,  540,  545 
Commissura  mollis,  see  Massa  intermedia, 

.542 
Completion    cavity,  see   also  Ergdnzungs- 

hohle,  59,  60 
Completion    plate,    see    also   Erganzungs- 

platte,  60,  63,  72 
Concha,  148,  151 
Conchas,  inferior,  196 
middle,  196 
superior,  196 
Cones,  508,  512,  582,  583 
Confluens  sinuum,  255 
Conjugation,  40 
Connective  tissue  follicle,  447 
tissues,  the,  165 
adipose,  171 
areolar,  170 
cartilage,  172 
development  of  the,  165 
embryonic,  170 

method  for  study  of,  217 
fibers  of,  171 
fibrillar  forms,  170 
ground  substance  of,  171 
histogenesis  of,  167 
intermuscular,  310 
osteogenetic,  175 
osseous,  173 
periosteum,  175 
Contractile  fibrils,  294 
Contractions,  rhythmical,  of  the  amnion, 

in  man,  1 16 
Convolutions     of     cerebral     hemispheres, 

549 
Coordination,  454 


Coordinating    centers,    higher,  see  Supra- 

segmental  structures, 
Coplin  jars  for  paraffin  sections,  636 
Coracoid  process,  203 
Cords,  medullary,  409 
Pfliiger's  egg,  411 
rete,  407 
sex,  408,  409. 
Cornea,  588 

elastic  membranes  of,  588 
endothelium  of  Descemet,  588 
membrane  of  Bowman,  588 
substantia  propria  corneae,  588 
Cornu  ammonis,  555,  559 
Corona  radiata,  1 1 

of  cerebral  hemispheres,  544 
Coronoid  process,  200 
Corpora  quadrigemina,  474,  524,  537 
anteria  brachia  of,  537 
layers  of,  537 
Corpus  albicans,  32 

callosum,  475,  550,  557,  565 
genu  of,  558 
splenium  of,  558 
haemorrhagicum,  32,  413 
luteum,  32,  413 
changes  in,  32 
false,  33 

of  pregnancy,  33 
true,  33 

Luysii,  544,  545 
sterni,  190 

striatum,  462,  474,  484,  485,  546,  548 
crura  of,  546,  548,  550 
tail  (cauda),  550 
Correus,  concerning  determination  of  sex, 

4i6,  439 

Cortex,  cerebral,  561 
Cortical  layer  of  telencephalon,    549 
Cortico-pontile   fibers    (of   the   pes),   473, 

478.  479.  531.  565 
Corti's  organ,  467,  474,  565,  597 
Costal  process,  184 
Cotyledon  (lobe),  131 
Cotyledons,  127 
Covering  layer  of  blastula  (trophoderm), 

see  also  Enveloping  layer,  52 
Cowper's  glands,  406 
Cranial  cavity,  development  of,  175 
Craniopagus,  610 
Craniopagus  parasiticus,  610 
Craniorachischisis,  618 
Cranior-rachischisis,  616 
Cranioschisis,  616,  619 
Crescentic  form  of  embryo,  144,  147 

groove,  of  Reptiles,  63 
Crescents  of  Gianuzzi,  330 
Cribriform  plate,  196 
Cricroid  cartilage,  201 
Crista  ampullaris,  596,  599 
Crista  galli,  196 
Crown-rump  length,  157. 
Crusta,  see  Pes  pedunculi 
Cryptophthalmia,  620 
Cuboid  cartilage,  208 
Culmen,  533 
Cumulus  ovigerus,  413 


646 


INDEX. 


Cuneiform  cartilages,  208 

ridge,  363 
Cuneus  of  cerebral  hemispheres,  561 

of  medulla,  53  i 
Cutis  plate,  75,  167,  168,  293 
Cutting  sections,  celloidin,  634 

paraffin,  634 

serial,  634 

Cuvier,  ducts  of,  227,  253 
Cyclocephaly,  620 
Cyclopia,  567,  6or,  610,  620 
Cyclostomus,  620 
Cyclotus,  620 

Cylinder  furrow  of  His,  516 
Cylindrical  form  of  body,  141 
Cystadenomata,  437 
Cystic  tumors,  613 
Cytoplasmic  plate,  8 
Cyto-trophoderm,  121,  125,  126 
Cysts,  436 

dermoid,  452 

sebaceous,  452 

Darkschewitsch,  nucleus  of,  524 
Darwin   and    Spencer,    concerning   fertili- 
zation, 40 
Daughter  cells,  3 

nuclei,  4,  6, 
Decidua,  120 

basalis,  124 

capsularis,  123 

parietalis,  123 
Decidual  cells,  127 
Decussation  of  Forel,  524 

of  Meynert,  537 
DeFormatione  Foetus,  XIII 
De  Formato  Fcetu,  XIII 
de  Graaf,  Regnier,  XIII 
de  Graaf,  Regnier,  concerning  the  Graaf- 

ian  follicle,  XIII 

Deiter's  nucleus,  tracts  from,  473,  518,  524 
Delafield's  haematoxylin,  635 
Dendrites,  492 

apical,  562 

of  pyramidal  cells,  563 
Dens,  the  (odontoid  process),  188 
Dental  groove,  324 

papilla,  324 

sac,  327 

shelf,  324 
Dentinal  canals,  327 

fibers,  327 

pulp,  324,  326 
Dentine,  324,  326 

formation,  327 
Dermal  navel,  105,  116 

umbilicus,  105 
Dermis,  the,  445 

arrectores  pilorum,  445 

pigment  of,  445 

tactile  corpuscles  of  Meissner  of,  445 

tunica  dartos,  445 
Dermoid  cysts,  452,  613 
Descemet,  membrane  of,  588 
Descent  of  ovary,  426,  441 
Descent  of  testicle,  423,  441 
Determinants,  29 


Determination  of  sex,  415 

epigamous,  415,  416 

progamous,  415 

syngamous,  415 
Deuterencephalon,  460 
Deutoplasm,  i,  12 
Dextrocardia,  285,  356 
Diaphragm,  the,  372,  377 

anomalies  of,  384 

caudal  migration  of,  378 

changes  in  position  of,  378 

ligaments  of,  378 

muscular  elements  of,  300 

primary,  376 

Diaphragmatic  hernia,  384 
Diaphysis,  180 
Diaplexus,  540 
Diarthrosis,  211 
Diastematomyelia,  618 
Diaster,  6 
Diatela,  540 
Dibrachius,  609 
Dicephalus,  610 
Didelphys,  uterus,  437 

Diencephalon   (inter-brain),  88,  462,  474, 
481,  485,  538  to  545 

epithalamus,  474,  475,  512,  543 

hypophysis,  474,  540 

hypothalamus,  474,  475,  485,  538,  540 

nuclei  of,  474 

Rathke's  pouch,  538 

sulcus  hypothalamicus,  538 

sulcus  Monroi,  538 

thalamus,  474,  485,  512,  543 
Differential  staining,  635 
Diffuse  nucleus,  2 
Digits,  beginnings  of,  147 

defects  or  absence  of,  623 
Diprosopus,  610 

diophthalmus,  610 
monostomus,  610 
tetrophthalmus,  610 
triophthalmus,  610 
Dipygus  parasiticus,  609 
Discoidal  placenta,  114 
Disse,  concerning  olfactory  nerve,  591 
Diverticulum  of    Nuck,  426 
Dollinger,  XIII 
Dorsal  flexure,  143 
Dorsal  mesogastrium,  380 

septum  of  spinal  cord,  517 
Dorso-, lateral  plate,  see  Alar  plate. 
Double  heart,  285 
Driesch,   concerning  potentiality  of  germ 

cells,  616 
"Dry"  labor,  117 
Ducts,  allantoic,  118,  338 

alveolar,  367 

cochlear,  596 

Cuvier's,  227,  253,  375 

cystic,  347 

deferent,  420 

ejaculatory,  420 

endolymphatic,  593 

hepatic,  347 

lacrymal,  589 

mesonephric,  389,  403 


INDEX. 


647 


Ducts,  Mullerian,  402,  417,  421 

of  the  epididymis,  420 

oviduct,  418 

pronephric,  387,  388 

reuniens,  596 

Santorini's,  3  52 

seminiferous,  405 

Steno's,  329 

thoracic,  278 

thyreoglossal,  333 

utriculosaccular,  596 

Wharton's,  329 

Wirsung's,  352 

Wolffian,  389 
Ductule,  aberrant,  421 

efferent,  421 
Ductus  arteriosus,  234,  246 

choledochus,  347 

pleuro-pericardiacus,  374 

venosus,  263,  349 
Duplicate  monsters,  605 

asymmetrical  duplicity,  612 

Marchand's   scheme  of,  605 

symmetrical  duplicity,  606 

teratoid  tumors,  606 

true  parasitic  duplicity,  612 
Duval,  concerning  formation  of  primitive 

streak,  65 
Duodenum,  the,  338,  339 

change  of  position  of,  382 
Duplicity  incomplete,  610 
Dyads,  17 
Dynamic  center,  8 

Ear,  457,  464,  469,  474,  513,  592 
anomalies  of,  60 1,  621 
cochlea,  467 

Corti's  organ,  467,  474,  565,  597 
external,  592,  600 
internal,  592 
labyrinth,  467 
middle,  592,  599 
practical    suggestions    for    study    of, 

603 
Ear,  inner, 

acoustic  nerve,  598 
atrium,  593 
auditory  pit,  592 

placode,  592 

vesicle  (otocyst),  592,  593 
cells  of,  598 
cochlear  pouch,  593 
ducts  of,  596 

endolymphatic  appendage  of,  593 
fenestra  cochleae  (rotunda),  597 

vestibuli  (ovalis),  597 
membrana  tectoria,  598 
organ  of  Corti,  597 
perilymph,  596 
perilymphatic  space,  596 
saccule,  596 
scala  media,  596,  597 

tympani,  596,  597 

vestibuli,  596,  597 
semicircular  canals  of,  593 
spiral  lamina,  597 
utricle,  596 


Ear,     inner,     vestibular     membrane     (of 
Reissner),  597 

vestibular  pouch,  593 
Ear,  middle,  599 

Eustachian  tube,  600 

incus,  599 

malleus,  599 

mastoid  cells,  600 

stapes,  599 
Ear,  outer,  600 

antitragus,  601 

anthelix,  60 1 

auricle,  600 

external  auditory  meatus,  600 

lobule,  60 1 

helix,  60 1 

tragus,  60 1 

tubercles  of,  60 1 

tympanum,  600 
Ectoderm  (epiblast),  55,   137 

formation  of,  55 

in  Amphibians,  58 

in  Amphioxus,  55,  56 

in  Birds,  64,  66 

in  frog,  60 

in  Mammals,  68 

in  Triton,  57,  58 

in  Reptiles,  62 

practical  suggestions  for  study  of,  96 
Ectopia  cordis,  215,  285,  384,  622 
Ectopia  vesicae,  622 
Ectopia  viscerum,  622 

of  the  kidneys,  433 
Ectoplasm,  174 
Ectopic  gestation,  31 
Edinger,  concerning  the  oral  sense,  475 
Effectors,  455,  458,  464 
Efferent  ductules,  420 

peripheral  nerve  fibres,  459 

peripheral    neurones,    454,    464,    493 
to  496 

root  fibers,  493 
Egg  (see  also  ovum),  10 

cleavage  in  hen's,  46 

diagram  of  hen's,  13 
Egg  nests,  411 

cords,  Pfliiger's,  411 

protoplasm,  1 1 
Eggs,  alecithal,  42,  43 

centrolecithal,  42,  45 

telolecithal,  42,  44,  46 
Eigenmann,  concerning  sex  cells,  407 
Ejaculatory  duct,  420 
Embedding,  with  celloidin,  633 

paraffin,  634 
Embryos,  abnormal,  i  58 

age  and  length  of,  155 

amphibian,  technic  for,  629 

chick,  technic  for,  630 

conclusions    of    His,    concerning    age 

of,  155 

gross  anomalies  of,  i  59 
human,  technic  for,  159,  631 
Mall's   formulae  for   deducing  age  of, 

157 
mammalian,   technic  for,  6?o 

normal,  1 58 


648 


INDEX. 


Embryos,  pathological,  i  58 

pig,  technic  for,  161,  630 

practical    suggestions   for   the    study 
of,  159 

rabbit,  technic  for,  63 1 

relation  of  age  to  length,   157 

transparency  of,  159 
Embryonal  bud  (inner  cell-mass),  68 
Embryonic  ccelom,  372 
Embryonic  connective  tissue,  170 

disk,  (see  also  Germ  disk),  13,46,  138, 

,    i39 

Enamel  organ,  324 
prisms,  325 

Pulp,  325 

Encephalocele,  617 
Encranius,  612 
End-brain  (telencephalon),  462,   474,    545 

to  568 

End  disk,  14 

Engastric  (intraabdominal)  parasites,  613 
End  knob,  anterior,  14 

posterior,  14 

Endocardium,  origin  of,  224 
Endolymphatic  duct,  593 

sac,  593 

Endomysium,  311 
End  ring,  14 
Entoderm  (hy poblast) ,  55 

formation  of,  55 

of  Amphibians,  58,  60 

of  Amphioxus,  55 

of  Birds,  62,  63,  64 

of  Mammals,  68 

of  man,  91,  94 

of  Reptiles,  62,  63,  64 

practical  suggestions  for  study  of,  96 

primitive,  137 

yolk,  58 

Entodermal  tube,  317 
Entrance  plug,  120 
Enveloping     layer,     see     Covering     layer 

(trophoderm),  137 
Eosin,  636 

Eparterial  bronchial  ramus,  367,  370 
Ependyma  cells,  488 
Epiblast  (see  also  Ectoderm),  55 
Epicanthus,  620 
Epichordal  brain,  lateral  series  of  nuclei 

of,  494,  495 

medial  series  of  nuclei  of,  494,  495 
Epichordal   segmental   brain  and   nerves, 

464,  466 

Epicondyles,  204 
Epidermis,  the,  7  5,  444 
epitrichium  of,  444 
periderm  of,  444 

practical  suggestion  for  study  of,  453 
stratum  corneum,  445 
germinativum  of,  444 
granulosum,  444 
lucidum,  445 

Bpididymis,  anomalies  of,  436 
appendage  of  the,  420 
duct  of,  420 

Epigamous  determination  of  sex,  415 
Epigenesis,  doctrine  of,  XIII 


Epiglottis,  363 
Epignathus,  612,  614 
Epimysium,  311 
Epiphyses  of  vertebrae,  187 
Epiphysis  of  bone,  180 

(pineal  body),  461,  474,  540 
Epiploic  foramen,  380 
Epispadias,  436 
Episternal  cartilages,  189 
Epistropheus,  the  (axis),  188 
Epithalamic  region,  see  Epithalamus 
Epithalamus,  474,  475,   512,   543 
Epithelium,  germinal,  406 

neuro-,  591,  596 
Epitrichium,  444 

practical  suggestion  for  study  of,  453 
Eponychium,  the,  447 
Epoophoron,  the,  419 
Equatorial  plate,  6 
Erganzungshole      (see      also      Completion 

cavity),  59 
Erganzungsplatte     (see     also    Completion 

plate),  60,  63 

Erythroblasts,  primitive,  271 
Erythrocytes,  272,  274 
Eternod's  embryo,  140,  480 
Ethmoidal  labyrinth,  196 
Eustachian  tube,  600 
Evagination,  mesodermic,  77 
Exencephaly,  617 
Exoccipital  bone,  194 
Exoccelom,  96,  139*,  372 
External  auditory  meatus,  origin  of,   147, 

J51 

ear,  first  appearance  of,  144 
form  of  the  body,  age  and  length  of 

embryos,  155 
development  of,  137 
extremities,  i  53 

branchial  arches,  face,  neck,  149 
methods  for  study  of,  160 
geniculate  bodies,  see  Geniculate  bodies 
genital  organs  (see  also  Genital  organs, 

external),  427 

genitalia,  first  appearance  of,  149 
influences  as  affecting  monsters,  624 

625 

Extraembryonic  body  cavity,  96,  139 
Extraventricular  cell-divisions,  492 
Extrauterine  gestation,  119 
Extremities,  development  of,  1 53 
lower,  fused,  623 
malformations  of,  622,  623 
muscles  of  the,  303 
nerve  supply  of,  304 
one  or   more   abnormally   small   but 

well  formed,  623 
one  or  more  defective,  623 
one  or  more  wanting,  623 
Eye,  457,  464,  466,  467,  474,  513,  573 
anomalies  of,  60 1,  620 
anterior  chamber,  588 
ciliary  body,  587 
chorioid,  585 
cornea,  588 

first  indication  of  formation  of,  574 
formation  of  muscles  of,  302 


INDEX. 


Eye,  general  development  of,  573 

jnfluence  on  nervous  system,  466 

innervation  of  muscles  of,  469 

iris,  587 

lens,  575 

muscles  of,  467 

optic  cup,  576,  579 

optic  depression,  573 
nerve,  586 

practical  suggestions  for  study  of,  692 

retina,  580 

sclera,  585 

vitreous,  585 
Eyelashes,  588 
Eyelids,  588 

Fabricius  ab  Aquapendente,  XIII 
Face,  development  of,  149,  589 

malformations  of,  152,  620 
Facial  cleft,  oblique,  621 
Facialis,  VII,  nerve,  469,  471 
"Faecal  fistula,"  117 
Falx  cerebri,  549 
Fascia,  origin  of  fibers  of,  171 
Fascia  dentata,  476,  555 
Fasciculi,  see  Tracts. 
Fasciculus  cortico-spinal,  478 

cuneatus,  see  Columns  of  Burdach 

dorsal  spino-cerebellar,  478 

frontal  cortico-pontile,  478 

gracilis,  see  Columns  of  Coll 

mammillo-tegmental,  544 

medial  longitudinal,  473,  511,  518,  523 

occipital  cortico-pontile,  478 

retroflexus  of  Meynert,  545 

solitarius,    see    Tractus   solitarius 

temporal  cortico-pontile,  478 

thalamomammillary,  544 

ventral  spino-cerebellar,  478 
Fat,  developing,  1.72 
Feet,  malformations  of,  623 
Female  pronucleus,  18 
Femur,  208 
Fenestra  cochleae,  597 

vestibuli  (ovalis),  597 
Fertilization,  35 

of  human  ovum,  40 

practical  suggestions  for  study  of,  41 

significance  of,  40 

Fertilized  ovum,  35 

derivation  of,  XIV 
Fibers,  afferent  peripheral  nerve,  458 

afferent  root,  458,  497 

arcuate  (external),  522 
(internal),  515,  522 

association  (see  also  Cells,  association) , 

563 

connective  tissue,  171 
cortico  pontile,  see  Cortico  pantile  fibres 
cortico-spinal,    see    Tracts,  pyramidal 
efferent  peripheral  nerve,  459,  493 

ventral  root  fibers,  493 
muscle,  294 
neuroglia,  490 

olivo-cerebellar,  473,  528,  536 
projection    (ascending    and    descend- 
ing), 477,  553,  562,  565 
Fibers,  spiral  of  spermatozoon,  14 


Fibers,  nerve,  various  views  concerning  de- 
velopment of,  500,  501 
visceral,  (splanchnic),  494,  498 
Fibrillogenous  zone,  491 
Fibrillar  connective  tissue,  170 
Fibula,  208 
Fila  olfactoria,  509 
Fillet,  lateral,  473,  478,  530,  537 

medial,  473,  478,. 527,  528,  537,  544,  564 
Filum  terminale,  519 
Fimbria,  555 
Fimbrias,  418 

Fingers,  development  of,  i  54 
Fissure,  anterior  arcuate,  547 
calcarine,  561 
callosal,  558 
central,  561 
great  longitudinal,  549 
of  Rolando,  561 
of  Sylvius,  560 
parieto-occipital,  561 
posterior  arcuate,  555 
prima,  of  His,  547 
primary,  of  cerebellum,  533 
secondary  of  cerebellum,  533 
rhinal,  medial  and  external,  547 
ventral  longitudinal,  517 
Fissures  of  cerebral  hemispheres,  549 
Fixation,  631 
alcohol,  631 
Bouin's  fluid,  631 
Carney's  fluid,  632 
Flemming's  fluid,  632 
formalin,  632 
Orth's  fluid,  632 
Gibson's  fluid,  632 
Perenyi's  fluid,  633 
Zenker's  fluid,  633 
Flechsig,    concerning   myelogenetic   areas 

of  pallium,  565,  566 
Flechsig's  tract,  478,  519 
Flemming,  concerning  amitosis,  4 

concerning  the   origin   of  connective 

tissue  fibers,  170 
Flemming's  fluid,  632 
Flexure,  cephalic,  143 
cervical,  144 
dorsal,  143 
sacral,  144 
Flocculi,  533 

Floor  plate  (ventral  median  plate),  460 
Foetal  inclusion,  612 
membranes,  99 
allantois,  106 
amnion,  99 
chorion,  107 

earlier   stages   in    Mammals,    com- 
pared with  chick,  108 
function  of,  99 
in  Birds,  99 
in  Mammals,  107 
in  man,  115 
in  Reptiles,  99 
practical  suggestions  for  study  of, 

135 

references  for  further  study  of,  136 
serosa,  107 


650 


INDEX 


Foetus,  the,  149 

in  foetu,  612 

papyraceus,  607 

Follicle,  Graafian,  rupture  of,  31 
Fontanelles,  198 
Foot,  development  of,  1 54 

,'-     veins  of,  266 
Foramen  caecum  linguas,  322,  332 

of  Magendie,  520 

of  Monro,  538,  546,  549,  553 

of  Winslow,  380 

ovale,  229 

transversarium,  189 
Foramina  of  Luschka,  521 
Fore-brain  (prosencephalon),  461,  464,  474 

anterior  (cerebral)  commissure,    461 

chiasma  eminence,  461 

commissura  habenularis,  462 

corpora  striata,  462 

diencephalon,  474 

epiphysis  of,  461 

ganglia  habenulae,  462 

lamina  terminalis  of,  461 

pallium,  462 

paraphysis  of,  461 

pineal  body,  461 

infundibulum,  461 

processus  neuroporicus,  461 

recessus  postopticus,  461 
praeopticus,  461 

rhinencephalon,  462,  474 

velum  transversum,  461 
Forel's  decussation,  524 
Formalin  for  fixation,  632 
Formatio  reticularis,  472,  518,  522  to  525 

alba,  523 

grisea,  523 
Fornix,    anterior   pillars    (columns),    476, 

544,  558 

body  of,  558 

commissure,  557 

posterior  pillar  (columns)  555,  558 

psalterium,  557 
Fornix  longus,   559 

Forster,  concerning  malformations,  605 
Froriep,  concerning  acustico-facialis  gang- 
lion, 598 

Fossa  Sylvii,  546,  547,  559 
Frenulum  linguas,  329 
Fretum  Halleri,  226,  232 
Frog,  cleavage  in,  44 

Frog's  eggs,  procuring  and  handling,  629 
Frontal  bone,  198 

lobe,  549 

Funiculus,  dorsal   (posterior)   or  posterior 
white  column,  497,  510,  514 

lateral,  518 

teres,  531 

ventral    (anterior)    or    ventral    white 
column,  514 

ventro-lateral,  514 
Furcula,  the,  363 

Galea  capitis,  14,  25 
Gall  bladder,  347 
Gartner,  canals  of,  420 
Ganglia,  cerebrospinal,  458 


Ganglia,  sympathetic,  ciliary,  508 

otic,  508 

peripheral,  498 

prevertebral  498 

sphenopalatine,  508 

submaxillary,  508 

vertebral,  498 

visceral,  466,  494 
Ganglion  acoustic,  598 
acustico-facialis,  598 
cochlear,  506,  598 
Gasserian,  467,  507 
geniculate,  505,  598 
habenulae,  462,  540 
interpeduncular,  545 
nodosum,  502 
petrosum,  502 
Scarpa's,  506,  (see  also  Nerves,  cranial, 

semilunar,  467,  507 
spinal,  497 
spirale,  506,  599 
vestibular,  506,  598 
Gasserian    ganglion,    peripheral    branches 

of,  467 

Gastral  mesoderm,  77 
Gastrointestinal     tract,     development     of 

glands  in,  344 
histogenesis  of  the,  343 
lymph  follicles  of,  345 
mucous  membrane  of,  343 
Gastroschisis,  313 
completa,  622 

Gastrothoracopagus  dipygus,  609 
Gastrula,  55 
Gastrulation,  in  Amphibians,  56 

yolk  content  in,  56 
in  Amphioxus,  55 

yolk  content  in,  55 
in  Birds,  61,  64 

yolk  content  in,  61 
in  hen's  egg,  64 
in  Mammals,  67 
in  man,  72,  89 
in  Reptiles,  61 

yolk  content  in,  61 
in  water  salamander — Triton  tasnia- 

tus,  57 

General  technic,  629 
embedding,  633 
fixation,  631 
hardening,  633 

methods  of  reconstruction,  637 
preservation,  633 

procuring  and  handling  material,  629 
section  cutting,  634 
staining,  635 
Geniculate  bodies,  lateral  (external),  477, 

_478,  512,  540,  562,  564,  586 
medial  (internal),  477,  478,  540,  562 
Geniculate  ganglion,  505 
Genital  cord,  423 
folds,  428 
glands,  the,  406 

differentiation  of,  408 

ducts  of,  417 

changes  in  the  positions  of,  421 


INDEX. 


651 


Genital  glands,  development  of    the  liga- 
ments of,  421 
migration  of,  423 
stroma  of,  407 
organs,  external,  427 
first  appearance  of,  149 
(female),  clitoris,  428 
glans  clitoridis,  428 
labia  majora,  428 
labia  minora,  428 
prepuce,  428 
vestibulum  vagina?,  428 
(male)  penis,  428 
prepuce,  428 
raphe,  430 
scrotum,  430 
urethra,  428, 
ridge,  392,  407,  427 

practical  suggestions  for  study  of, 

440 

swellings,  428 
tubercle,  the,  428 
Gennari,  line  of,  564 
Genu  facialis,  524 
Germ  disk,  13,  46 
of  Birds,  46 
of  Reptiles,  64 
hill,  n,  413 
layers,  55 

diagram  showing,  58 

the  ectoderm,  55 

the  entoderm,  55 

the  epiblast,  55 

the  hypoblast,  55 

in  man,  89 

the  mesoderm,  72 

practical  suggestions  for  study  of, 

96 

primary,  55 
German   method   of   measuring   embryos, 

156 
Germinal  disk,  see  also  Germ  disk,  13 

epithelium,  407 
cells  of,  407 
rete  cords  of,  407 
sex  cords  of,  408 

spot,  12 

Gianuzzi,  crescents  of,  330 
Giant  glomeruli,  402 
Gibson's  fluid,  632 

Gill  arches,  musculature  of,  311,  466 
Gill-cleft  organs,  459 
Gills,  influence  on  nervous  system,  466 
Giraldes,  organ  of,  421 

Giron,  concerning  determination  of  sex,  416 
Glands,  accessory  thyreoid,  333 

anterior  lingual,  329 

Bartholin's,  406 

Brunner's,  344 

bulbo-urethral,  406 

carotid,  433 

coccygeal,  285 

Cowper's,  406 

duodenal,  344 

Ebner's,  323 

formation  of,  344 

genital,  406 


Glands,  haemolymph,  281 

indifferent  (genital),  410 

lacrymal,  588 

lingual,  323 

liver,  346 

lymph,  279 

mammary,  449 

Meibomian,  588 

of  Mall,  588 

parotid,  329 

prehyoid,  333 

salivary,  328 

sebaceous,  449 

sublingual,  329 

submaxillary,  328 

sudoriferous,  449 

suprahyoid,  333 

suprarenal,  430 

sweat,  449 

thymus,  334 

thyreoid,  332 

uterine,  419 

vestibular,  406 
Glans  clitoridis,  428 

penis,  428 
Glia,  see  Neuroglia 
Glisson,  capsule  of,  347,  376 
Glomeruli  of  kidney,  396,  397 
Glomus  caroticum,  336,  433 

coccygeum,  285 
Glossopalatine  arch,  331 
Glossopharyngeus,  IX,  nerve,  469 
Golgi  methods  of  staining,  568 
Goll,  column  of,  466,  478,  517,  525 

nuclei  of  columns  of,  466,    473,    474, 

527 
Graafian  follicle,  411,  412 

primary,  410,  411 

de  Graaf's  description  of,  XIII 
Graf  v.  Spee's  ovum,  90 
Granules,  keratin,  446 
Graphic  reconstruction,  637 
Gray      column      (dorsal      or      posterior), 

465 

(ventral  or  anterior),  465,  514 
matter  of  cord  and  segmental  brain, 

511 

ramus  communicans,  499 
Ground  bundles  of  the  cord,  472,  511,  514, 

516,  523,  525 
Growth  of  bones,  180 

intracartilaginous,  180 

long,  1 80 

Gubernaculum  testis,  422,  423 
Gulland,  concerning   origin   of   lymphatic 

vessels,  276 

Gurwitsch,   concerning  peripheral  nerves, 
500 

concerning  the  myelin  sheath,  501 
Gustatory  area,  565 

system,  459,  467 

Gyri,  transverse  of  temporal  lobe,  564 
Gyrus  ambiens,  548 

dentatus,  476,  555,  558 

olfactorius  lateralis,  548 

semilunaris,  548 

subcallosus,  559 


652 


INDEX. 


Habenula,  540 
Haemoglobin,  271 
Hagmangiomata,  452 
Haematopoietic  function,  271 
Haematoxylin,  Delafield's,  635 

Heidenhain's,  636 

Weigert's,  570,  635 
Hasmolymph  glands,  281 
Hair,  the,  447 

anomalies  of,  452 

cells,  596,  598,  599 

connective  tissue  follicle  of,  447 

Henley's  layer,  447 

Huxley's  layer,  447 

lanugo  the,  447 

practical  suggestions  for  study  of, 

453 

germs,  447 
papilla,  447 
shaft,  447 
Hamatate,  205 
Hammar,    concerning  the  tuberculum  im- 

par,  322 
Hands,  development  of,  1 54 

malformations  of,  623 
Hardening  tissues,  633 
Hardesty,     concerning     development     of 

neuroglia,  486 
Hare-lip,  200,  216,  620,  621 
Harrison,     concerning    neurilemma    cells, 

500 

Harvey,  XIII 
Hassall's  corpuscles,  335 
Ha versian  canals,  179 
lamellae,  179 
spaces,  179 
Head,  beginning  of,  142 

somatic  musculature  of  (eye,  tongue) , 

innervation  of,  469 
amniotic  fold,  too 
cap,  14 
fold,  83 
process  (primitive  intestinal  cord)  in 

the  chick,  66 
in  Mammals,  70 
skeleton,  190 

anlagen  of,  191,  193 

anomalies  of,  215 

bones   derived   from  the  branchial 

arches,  198 
cartilage  of,  191 
cartilaginous    primordial   cranium, 

192 

chondrification  of,  191 
chondrocranium,  193 
diagram  of  skull  of  new-born  child, 

197 

membrane  bones  of  the  skull,   196 
ossification  of  the  chondrocranium, 

194 

periotic  capsule,  193 
practical     suggestions    for    further 

study  of,  218 
table  showing  types  of  development 

of  bones  of,  202 
Heart,  the,  222 

anomalies  of,  285,  607 


Heart  beat,  234 

changes  after  birth,  233 
development  of,  225 
double,  285 

double  origin  in  all  lower  forms,  225 
first  indications  of,  143 
interventricular  furrow,  226 
migration  of,  374,  377 
muscle,  histogenesis  of,  311 

practical  suggestions  for  study  of, 

•   -3I§ 
origin  of,  223 

practical  suggestions  for  study  of,  291 

primitive,  222 

return  of  blood  to,  2  59 

septa  of,  229 

simple  cylindrical,  225 

sinus  venosus,  227 

valves,  231 
Heidenhain's  hasmatoxylin,  636 

staining  with,  637 
Held,    concerning    early    development    of 

neurofibrils,  491 
Helix,  60 1 

Hemicrania,  616,  617 
Hemispheres  of  cerebellum,  533 
Hemispheres,  cerebral,  464,  477,  481,  545, 

548  to  567 
Henle's  layers,  447 

!oop,  397 
Hensen,     concerning     peripheral     nerves, 

501 
Hensen's  cells,  598 

node,  65,  70,  91 
Hepatic  cords,  3  50 

portal  system,  259 
Hepatoduodenal  ligament,  382 
Hepatogastric  ligament,  382 
Heredity,  important  factor  in  teratogene- 
sis,  624 

in  relation  to  anomalies  of  muscular 
system,  314,  315 

influence  of,  in  albinism,  452 
Hermaphroditism,  438 

bilateral,  438 

false,  438 

feminine  false,  438 

lateral,  438 

masculine  false,  438 

true,  438 

unilateral,  438 
Hernia,  diaphragmatic,  384 

umbilical,  117 
Herrick,  concerning  the  gustatory  tracts, 

475 

concerning  gustatory  pathway,  526 
Hertwig,  concerning  duplicity  from  double 

gastruke,  612 

concerning  the  formation  of  the  prim- 
itive streak,  65 

concerning  the  mammary  gland,  450 
concerning    mesoderm    formation    in 

Triton  and  Amphioxus,  77 
concerning  spina  bifida,  619 
on  production  of  monsters,  626 
Heteromeric  column  cells,  510 
Hind  brain  (metencephalon),  462 


INDEX. 


653 


Hippocampal  fissure,  555 

formation,  476,  550,  555  to  559 

Hippocampus  major,  555,  559 

His,    concerning   age   and   length   of   em- 
bryos, 155 
concerning    angulus    praethalamicus, 

547 

concerning  germinal  cells,  486 
concerning      limbus      corticalis      and 

medullaris,  549 
concerning  neuroblasts,  492 
concerning  olfactory  nerve,  591 
concerning  peripheral  nerves,  501 
cylinder  furrow  of,  516 
marginal  furrow  of,  516 
trapezoid  area  of,  548 
Hochstetter,    concerning  the  bucco-nasal 

membrane,  589,  590 
Holorachischisis,  617 
Horns,    anterior    (ventral    gray    column), 

465,  5J4 

Horseshoe  kidney,  433 

Howell    and    Wright,    concerning    mega- 
karyocytes  and  blood  plates,  276 
Howslip's  lacunas,  176 
Human  embryos,  technic  for,  i  59,  63  i 
Humerus,  204 

Hunteri,  gubernaculum,  423 
Huntington  and  McClure,  concerning  con- 
nection   of    lymph    vessels    with 
veins,  278 

concerning  venous  loop  (supracardinal 

vein),  261 
Huxley's  layer,  447 
Hyaloid  canal,  586 

membrane  of  vitreous,  585 
Hyaloplasm,  i 
Hydatid  of  Morgagni,  421 

non-stalked,  418 
Hydramnios,  1 1 6 
Hydrencephaly,  617 
Hydrencephalocele,  617     . 
Hydrocephaly,  congenital,  617 
Hydromeningocele,  617 
Hydromicrencephaly,  617 
Hymen,  the,  419 

anomalies  of,  438 
Hyoid,  201 
Hyoid  arch,  471 
Hyperkeratosis,  451 
Hypermastia,  452 
Hyperthelia,  452 
Hypertrichosis,  452 
Hypoblast  (see  also  Entoderm),  55 

formation  of,  55 
Hypochordal  bar,  188 
Hypoglossus,  XII,  nerve,  469,  522 
Hypophyseal  pouch,  538 
Hypophysis,  474,  540 
Hypospadias,  436 

Hypothalamic  region,  see  Hypothalamus 
Hypothalamus,  474,  475,  485,  538,  543 
Hypotrichosis,  452 

Ichthyosis,  451 

Ids,  29 

Imperf orate  hymen,  438 


Ilium,  the,  207 
Incisive  bone,  199 
Incisura  prima,  547 
Incus,  201,  599 
Indifferent  glands,  410 

anomalies  derived  from,  438 

stage,  diagram  showing,  427 

table    showing    structures    derived 
from,  427 

structures,  408 
Indusium  griseum,  558 
Infracardiac  ramus,  368 
Infundibular  process,  539 
Infundibulum,  461,  485,  538 
Inguinal  ligament,  422 

ring,  the,  424 
Iniencephaly,  617 
Inner  cell  mass,  52,  137 

layer  of  neural  tube,   492,    509,  521, 

534,  537,  549,  561 
Innominate  artery,  245 

bone,  207 

veins,  2  56,  2  57 
Insula  (island  of  Reil),  559 
Integumentary  system,  the,  444 

anomalies  of,  451 

glands  of  the  skin,  449 

hair,  447 

nails,  446 

practical  suggestions  for  study  of,  453 

skin,  444 
Inter-brain      (diencephalon),      see     Dien- 

cephalon 

Intercarotid  ganglion,  433 
Intercellular  substance,  origin  of,  169 
Intermediary  plexus  of  lymph  glands,  280 
Intermediate  areas  of  Flechsig,  565 

cell  mass,  84 

(medullary)    layer    of    telencephalon, 

549 

plate,  516,  518 

Intermuscular  connective  tissue,  310 
Internal   capsule  of   fore-brain,  479,   544, 
552,  553,  565 

geniculate  bodies,  see  Geniculate  bodies 
Interrenal  organs,  432 
Interventricular  furrow,  226 
Intervertebral  fibrocartilage,  184,  188 
Intervillous  spaces,  131 
Intestinal  crypts  of  Lieberkiihn,  344 

region,  .318 

tract,  colon,  339,  341 
duodenum,  339 

mesenterial  small  intestine,  339 
vermiform  appendix,  342 

umbilicus,  105 
Intestine,  the,  338 

anomalies  of,  3  58 

crypts  of  Lieberkiihn,  344 

loops  of,  339,  340 

practical  suggestions  for  study  of,  359 

villi  of,  344 
Iris,  587 

defective  pigmentation  of,  452 
Ischiopagus,  608 

parasiticus,  609 
Ischiothoracopagus,  609 


654 


INDEX. 


Ischium,  the,  207 
Island  of  Reil,  559 
Islands  of  Langerhans,  355 
Isthmus,  462,  520 
Iter,  see  Aquczductus  Sylvii 

Jacobson's  organ,  591 
Janus  asymmetros,  610 

symmetros,  610 
Jaws,  malformations  of,  620,  621 

splanchnic  musculature,   innervation 

of,  469,  471 

Johnston,  concerning  mesencephalic  root 
of  V,  530 

concerning  the  optic  recess,  538 
Joint    capsule,  211 

cavity,  211 
Joints,  209 

diarthrosis,  211 

synarthrosis,  210 

synchondrosis,  210 

syndesmosis,  210 
Jugular  lymph  sac,  277,  278 
Kallius,  concerning  the  mammary  gland, 

449 

Karyoplasm,  i 
Karyosomes,  i 

Keibel,  concerning  origin  of   endolymph- 
atic  appendage  in  the  chick,  593 
Keratin  granules,  446 
Kidney,  the,  394 

anomalies  of,  433 

Bowman's  capsule,  398 

capsule  of,  401 

changes  in  position  of,  402 

columns  of  Bertini,  400 

congenital  cysts  of,  434 

convoluted  tubule,    Henle's  loop   of, 

397 

cortex  of,  401 
derivation  of,  394 
floating,  434 
glomeruli  of,  396 

and  blood  vessels  of,  397 
hilus  of,  400 

Malpighian  pyramids  of,  400 
medulla  of,  401 
metanephric  blastema  of,  395 
migration  of,  402 
movable,  434 
nephrogenic  tissue  of,  395 
practical  suggestions  for  study  of,  440 
relation  to  suprarenal  gland,  432 
renal  columns  of,  400 

corpuscle  of,  400 

papilla;  of,  396,  401 

pelvis,  394 

pyramids  of,  400 

tubules  of,  convoluted,  396 

tubules  of,  straight,  395 
revehent  veins  of,  2  58 
ureter,  394 

urinary  function  of,  402 
Knower,    H.    McE.,    concerning   injecting 
blood-vessels  with  India  ink,  291 
on  production  of  monsters  in  single 
embryos,  626 


Kolliker,  XIV 

concerning  formation  of  incisive  bone, 

200 

Krause,  concerning  origin  of  endolymph- 
atic  appendage  in  chick  and  Am- 
phibia, 593 

Kupffer,  v.,  concerning  the  acoustic  gang- 
lion, 598 
concerning  the  differentiation  of  the 

neural  tube,  460 
concerning  olfactory  placodes,  589 


Labia  majora,  428 

minora,  428 
Lacrymal  bone,  198 

duct,  589 

glands,  588 
Lacunae,  175 
Laloo,  609 
Lamella;,  Haversian,  179 

interstitial  179 
Lamina  affixa,  557 

cribrosa  (of  eye),  587 
(of  nose),  196 

lateral  pterygoid,  198 

infrachorioidea,  554,  555 

medial  pterygoid,  197 

perpendicularis,  196 

terminalis,  461,  546,  554 
Langerhans,  islands  of,  355 
Langhan's  layer,  125 

outgrowths  from,  126 
Lanugo,  the,  447 
Laryngeal  pouch,  363,  370 
Larynx,  the,  363 

anomalies  of,  370 

cartilages  of,  364 

development  of,  201,  363 
Lateral  geniculate  bodies,   see  Geniculate 
bodies 

lemniscus,  473 

line  cranial  nerves,  469 
organs,  458,  459,  467,  469 

nasal  process,  1 52 

plate  (of  mesoderm),  75 

plates  (of  neural  tube),  460 

recesses  of  fourth  ventricle,  520 
Leg,  development  of,  i  54 
Lemmocytes,  499 
Lemniscus,  lateral,  see  Fillet,  lateral 

medial,  see  Fillet,  medial 

Lens.  575 

anterior  epithelium  of,  577 

area,  575 

capsule,  579 

fibers  of,  577 

hyaloid  artery  of,  579 

invagination,  575 

membrana  pupillaris  of,  579 

tunica  vasculosa  of,  579 

vesicle,  575 

Leopold,  concerning  ovulation  and  men- 
struation, 31 

ovum  of,  89 
Leucoblasts,  274 
Leucocytes,  181,  274,  275 


INDEX. 


655 


Leucocytes,  mononuclear,  275 
'  polymorphonuclear,  275 

poly  nuclear,  275 
Lewis,  concerning  anomalies  of  pancreas, 

359 

concerning  origin  of  lymphatic   ves- 
sels, 277,  278 

Lieberkuhn,  crypts  of,  344 
Life  cycle,  complete,  in  the  female,  413 

complete,  in  the  male,  415 
Ligaments,  broad,  of  the  uterus,  426 

costo- vertebral,  188 

diaphragmatic    of   the    mesonephros, 
422 

hepatoduodenal,  382 

hepatogastric,  382 

inguinal,  422 

middle  umbilical,  119,  404 

origin  of  fibers  of,  171 

ovarian,  426 

round,  of  liver,  265 
of  uterus,  426 

sphenomandibulor,  200 

stylohyoid,  201 

suspensory  of  the  lens,  588 

umbilical,  250 
Ligamentum  arteriosum,  234,  246 

coronarium  hepatis,  378 

suspensorium  (falciforme)  hepatis,  378 

teres  hepatis,  378 
Limb  bud,  lower,  145,  153,  306 

upper,  145,  153,  304 
Limb  buds,  differentiation  of,  304,  306 
Limbus  corticalis  of  His,  549 

fossae  ovalis,  232 

medullaris,  549 
Lingual  glands,  323 

papillae,  322 

tonsils,  331 
Lingula  (of  cerebellum),  533 

(of  sphenoid),  195 
Linin,  i 
Lip,  clefts  of,  200,  216,  620,  621 

lower,  origin  of,  148 

upper,  origin  of,  148 
Liquor  amnii,  102 
Liquor  folliculi,  412 
Liver,  the,  346 

anomalies  of,  3  58 

bile  capillary  of,  3  50 

capsule  of  Glisson,  347 

cells  of,  3  50 

circulation  of,  347 

ducts  of,  347 

gall  bladder  of,  347 

growth  of,  3  50 

haematopoietic  function  of,  272 

hepatic  cylinders  of,  348 

histogenesis  of,  3  50 

lobe  of  Spigelius,  350 

lobes  of,  349 

pars  hepatica  of,  346 
cystica  of,  346 

practical  suggestions  for  study  of,  360 

round  ligament  of,  265,  350 

vasa  aberrantia  of,  351 

veins  of,  262,  349 
42 


Lobus  pyriformis,  476,  548 

Loeb,  concerning  production  of  monsters, 

626 

Longitudinal  fasciculus,  medial,  473 
Lordosis,  616 
Lower  extremities,  207 
Lumbar  enlargement,  466 
Lunate  bone,  204 
Lung  groove,  362 
Lungs,  the,  366 

anomalies  of,  370 

atria  of,  367 

changes  in,  at  birth,  369 

ducts  of,  367 

eparterial    bronchial  ramus  of,   367, 

37° 

influence  on  nervous  system,  466 
lobes  of,  367 

practical  suggestions  for  study  of,  370 
weight  of,  369 
Lunula,  the,  447 
Luschka,  foramina  of,  521 
Lutein  cells,  or  granules,  32 
Lymph,  origin  of,  282 
follicles,  284 

of  gastrointestinal  tract,  345 
of  tonsils,  331 
glands,  the,  279,  282,  346 
methods  for  study  of,  291 
hearts,  276 
sacs,  276 

Lymphangiomata,  452 
Lymphatic  system,  the,  276 
glands  of,  279 
glomus  coccygeum,  285 
practical  suggestions  for  study  of, 

290,  291 
spleen,  282 
thymus  gland,  285 
vessels  of,  276 
vessels,  systemic,  276,  279 
Lymphocytes,  271,  272,  273,  274,  280 
Macromeres,  50 
Macrostomus,  621 
Macula  acustica,  599 
Macula  lutea,  582 
Magendie,  foramen  of,  520 
Magna-reticulare,  i  59 
Malformation    involving    one    individual, 

see  Monsters,  616 

Malformations  of  more  than  one  in- 
dividual, see  Duplicate  monsters, 
605 

Mall,  concerning  connective  tissues,  169 
concerning  development  of  the  max- 
illa, 199 
concerning  development  of  pyramids, 

562 
concerning     ossification     of     incisive 

bone,  199 

formulae   for   estimating   age   of   em- 
bryos, 157 
on  faulty  implantation  of  the  ovum, 

627 

on    theories    of   production   of   mon- 
sters, 624 
Malleus,  201,  599 


656 


INDEX. 


Mallory  and   Wright's  pathological  tech- 

_nic,  571 
Malpighian  corpuscle,  390 

pyramids,  400 

Mammalian  embryos,  technic  for,  630 
Mammary  gland,  the,  449 

anomalies  of,  452 

areolar  glands  of,  450 

colostrum  corpuscles,  451 

growth  of,  in  female,  450 

growth  of,  in  male,  4  50 

nipple,  450 

of  pregnancy,  450 

practical  suggestion  for  study  of,  453 
Mammillary  bodies,  540 

region,  485,  540 
Mandible,  200 

Mandibular  process,  144,  151,  319 
Mantle  fibres,  6 

layer  of  neural  tube,  492,   509,    521, 

.  534,  537,  549,  561 
Manubrium  sterni,  190 
Marchand's  fusion  theory  of  symmetrical 

duplicity,  611 

scheme  of  duplicate  monsters,  605 
Marginal  furrow  of  His,  516 
Marginal  layer  of  neural  tube,  486,    521, 

534,  537,  549 
Marrow,  181 

cavity,  primary,  177 

formation  of  blood  cells  in,  273,  274,  275 

red,  182 

spaces,  primary,  175 

yellow,  182 
Marsupials,  early  nutritional  conditions  in, 

112 

Masculine  false  hermaphroditism,  438 
Massa  intermedia,  542 
Mastoid  process,  195 
Maternal  impressions,  624 
Maturation,  17 

in  Ascaris,  17 

of  male  sex  cells,  2 1 

of  the  ovum,  17 

practical  suggestions  for  study  of,  33, 

34 

Maxilla  bone,  198 

Maxillary  process,  144,  151,  319 

McClung,  concerning  determination  of  sex, 
4i6,  439 

McClure  and  Huntington,  concerning  con- 
nection   of    lymph  vessels  with 
veins,  278 
concerning  supracardinal  vein,  261 

McMurrich,  concerning  arteries,  252,  253 
concerning  derivation  of  the  dermis, 

445. 

concerning  umbilical  cord,  133 
Mechanical  theory  of  monsters,  625 
Meckel's  cartilage,  193,  198,  200 

diverticulum,  117,  340 
Medial  fillet,  see  Fillet,  medial, 

geniculate     bodies,      see      Geniculate 

bodies 

lemniscus,  see  Fillet,  medial 
longitudinal  fasciculus,  473,  511,  518, 
523.  524 


Medial  nasal  process,  1 52 
Mediastinum  testis,  415 
Medulla  oblongata,  484,  519 

taenia  of,  520 
Medullary  cords,  409,  410 

folds,  in  chick  blastoderm,   67 

groove,  71 

layer  of  telencephalon,  549,  561 

sheath,  see  Myelin  sheath 
Megakaryocytes,  275,  276 
Megaloblasts,  272,  273,  274 
Meibomian  glands,  588 
Meissner,  plexus  of,  498 

tactile  corpuscles  of,  445 
Membrana  preformativa,  326 

tectoria,  598 

undulatoria,  i  5 

Membrane  bones  of  the  skull,  196 
Meningocele,  617 
Meningoencephalocele,  617 
Menstruation,  30 

relation    to    fertilization,  3 1 

relation  to  ovulation,  30 
Merkel,  concerning  the  origin  of  connect- 
ive tissue  fibers,  170 
Merocytes,  63 
Merorachischisis,  618 

Mesencephalon  (mid-brain),   88,  461,  482 
Mesenchymal  tissue,  169 

differentiation  of,  304 
Mesenteries,  372,  379,  382 

anomalies  of,  384 

practical  suggestions  for  study  of,  385 
Mesenterial  small  intestine,  339 
Mesentery  of  the  jejunum,  382 
Mesoappendix,  383 
Mesocardium,  dorsal,  223,  374 

ventral,  223,  374 
Mesocolon,  ascending,  383 

descending,  383 

sigmoid,  383 

transverse,  382 
Mesoderm,  derivatives  from,  165 

development  of,  138 

extraembryonic,  92 
orgin  of,  94 

formation  in  Amphibians,  76 
in  Amphioxus,  72 
in  Birds,  79 
in  the  frog,  77 
in  Mammals,  85 
in  man,  90,  92,  95,  96 
in  Reptiles,  78 

gastral,  77 

intraembryonic,  92 
origin  of,  95 

layers  of,  in  von  Spec's  embryo,  92 

parietal,  75,  138,  372 

peripheral,  87 
origin  of,  95 

peristomal,  58,  77 

splanchnic,  106,  343 

visceral,  75,  87,  138,  372 
Mesodermic  evagination,  77 

somites,  72,  143,  293,  300 
Mesoduodenum,  382 
Mesogastrium,  dorsal,  336,  379 

ventral,  337,  379 


INDEX. 


657 


Mesonephric  duct,  389 

mesentery,  422 
Mesonephroi,  atrophy  of,  in  the  female,  419 

in  the  male,  420 
Mesonephros,  389 

Bowman's  capsule,  390 

degeneration  of,  393 

diaphragmatic  ligament  of,  392,  422 

disappearance  of,  393 

function  of,  392 

glomerulus  of,  390 

Malpighian   corpuscle  of,  390 

practical  suggestions  for  study  of,  439 

renal  portal  system  of,  393 

significance  of,  393 

tubules  of,  389 
Mesorchium,  409,  423 
Mesonephric  ridge,  388,  391 
Mesorectum,  383 
Mesothelium,  372,  427 
Mesosalpinx,  420,  426 
Mesovarium,  409,  423,  426 
Metacarpals,  205 
Metanephric  blastema,  395 
Metanephros,  see  Kidney 
Metaphase,  6 
Metaplasm,  i,  2 
Metaplexus,  520 
Metapore,  520 
Metatarsals,  209 
Metathalamic    portion    of  thalamus,   543, 

553 
Metathalamus,    see    Metathalamic   portion 

of  thalamus 

Metencephalon (hind-brain),  88,  462 
Method  of  measuring  embryos,  American, 

'57 

German,  1 56 
Metopic  suture,  198,  216 
Metopism,  216 
Meyer,     concerning     mesencephalic     root 

of  V,  530 
Meyer,  Adolf,  concerning  segments  of  seg- 

mental  brain  and  cord,   512,   513 
concerning  suprasegmental  and   seg- 

mental  structures,  457,  464 
Meynert,  solitary  cells  of,  565 
Meynert's  decussation,  537 
Micrencephaly,  617 
Microbrachius,  623 
Microcephaly,  617 
Micrognathus,  357,  621 
Micrognathy,  357,  621 
Micromelus,  623 
Micromeres,  50 
Microphthalmia,  60 1,  620 
Micropus,  623 
Micropyle,  38 
Microstomus,  621 
Mid-body,  8 

Mid-brain  (mesencephalon),  461,  482 
optic  lobes,  462 
roof,  464,  474 

descending  tracts  to  after  brain  and 

cord  segments,  474 

Middle  peduncle  of  cerebellum,  473,  478, 
.    48o,  530,  537 


Milk  ridge,  the,  449 

method  of  studying,  453 
teeth,  324,  327 
Mimetic  musculature  and  its  innervation, 

47i 

Minot,  concerning  circulation  of  blood,  259 
concerning  fcetal  membranes  of  um- 
bilical cord,  133 

Mitoses,    see    also    Cell    proliferation    and 
Geminal  cells,  486,  521,  526,  543 
extraventricular,  492 
of  neural  tube  cells,  486,  537 
Mitosis,  4 

diagrams  of  successive  stages  of,  5,  7 
of  mucous  cells  of  stomach,  345 
phases  of,  4 

practical  suggestions  for  study  of,  9 
multipolar,  9 
pluripolar,  9 
Mitotic  division  of  sex  cells,  407 

figure,  6 
Mitral  cells,  512 
Monaster,  6 
Monobrachius,  623 
Monochorionic  quadruplets,  611 
triplets,  611 
twins  (equal),  606,  607 

(unequal),  607 
Mononuclear  leucocytes,  275 
Monopolar  cells,  492 
Monopus,  623 
Monotremes,  early  nutritional  conditions 

in,  112 

Monro,  foramen  of,  538,  546,  549,  553 
Monsters,  amniotic  adhesions,  623 
causes  underlying  origin  of,  624 
defects  in   region   of  face  and   neck, 

and  their  origin,  621 
defects  in  region  of  neural  tube,  616 

origin  of,  619 
defects  in  the  thoracic  and  abdominal 

regions,  and  their  origin,  622 
in  single  embryos,  626 
malformations  of  extremities,  622 

polysomatous,  625 
production  of  duplicate,  625 
Montgomery,    concerning   areolar  glands, 

45° 

Morgagni,  hydatid  of,  421 
liquor,  577 

non-stalked  hydatid  of,  418 
Morgan,  concerning  determination  of  sex, 

416,  439 
concerning    development    of    blasto- 

meres,  612 
concerning  production  of  spina  bifida, 

626 

Morula,  42,  49,  51,  137 
Mossy  fibers,  537 
Motor  cortex  (see  also  Pallium,  precentral 

area  of),  565 
Mouse,  cleavage  in,  51 
Mouth,  the,  318 

angle  of  the,  145,  152,  319 
anomalies  of,  357 
development  of,  320 
influence  on  nervous  system,  466 


658 


INDEX. 


Mouth,  origin  of,  318 

practical  suggestions  for  study  of,  3  59 
Mouth  slit,  i  52 
Mucous  tissue,  133 
Mulberry  mass,  49 
Miillerian  ducts,  402,  417 

atrophy  of,  421 
Multiple  placenta?,  114 
Multiplicity,  61 1 

Muscle,  heart,  histogenesis  of,  311 
Muscles,  differentiation  of,  305 
innervation  of,  294 
practical  suggestions  for  study  of,  315 
of  the  extremities,  303 
derivation  of,  303 

derivation  from  premuscle  sheath  of 

muscles  of  lower  extremity,  306 

differentiation   from   mesenchymal 

tissue,  304 

extrinsic  muscles,  305 
migration  of,  306 
of  the  head,  300 

chondroglossus,  303 

constrictor  muscles  of  the  pharynx, 

3°3 
development   and    innervation   of, 

302 

digastricus,  302,  303 
epicranius,  303 
glossopalatinus,  303 
laryngeal,  303 
masseter,  302 
mentalis,  303 

muscles  of  the  soft  palate,  303 
mylohyoideus,  302 
obliquus  inferior,  302 

superior,  302 
platysma,  303 

quadratus  labii  superioris,  303 
recti  inferior,  302 

medialis,  302 

superior,  302 
rectus  lateralis,  302 
pterygoidei,  302 
risorius,  303 
stapedius,  303 
sternomastoidcus,  303 
stylohyoideus,  303 
stylo-pharyngeus,  303 
temporalis,  302 
tensor  tympani,  302 
tensor  veli  ^alatini,  302 
trapezius,  303 
triangularis,  303 
of  the  trunk,  295 
coccygeus,  300 
geniohyoideus,  299 
intercostales,  298 
levator  ani,  300 
longus  capitis,  298 
longus  colli,  298 
obliqui  abdominis,  298 
omohyoideus,  299 
perineal,  300 
psoas,  298 
pyramidalis,  299 
quadratus  lumborum,  298 


Muscles,  rectus  abdominis,  299 

capitis  anterior,  298 
sacrospinal,  300 
scaleni,  298 

sphincter  ani  externus,  300 
sternohyoideus,  299 
sternothyreoideus,  299 
transversus  abdominis,  298 

thoracis,  298 
branchiomeric,  302 
extrinsic,    of    the    upper    extremity, 
anomalies  of,  314 
lattissimus  dorsi,  305 
levator  scapulae,  305 
pectoralis,  305 
serratus,  305 
trapezius,  305 

Muscle  fibers,  change  of  direction  of,  295 
practical  suggestions  for  study  of, 

315 

theories  concerning  internal  struc- 
ture of,  308 
plates,    1 68,  294 

formation  from  primitive  segment, 

75 

tissue,  histogenesis  of  striated  volun- 
tary, 307 
practical  suggestions  for  study  of, 

3i5 

smooth,  311 

Muscular  system,  the,  293 
amomalies  of,  313 

practical  suggestions  for  study  of,  314 
skeletal  musculature,  293 
visceral  musculature,  293,  311 
Musculature,  hyoid,  302 
skeletal,  293 

diaphragm,  the,  300 

early  character  of,  293 

loss    of    segmental   character,   294, 

2Q5 

muscles  of  the  extremities,  303 
of  the  head,  300 
of  the  trunk,   295 
myotomic  origin,  293,  300,  303 
visceral,  311 

mesodermic  origin  of,  3 1 1 
Myelencephalon     (after-brain),     88,     462, 

5J9 

Myelin  sheath,  485,  501 
Myelocystocele,  618 
Myelocytes,  182,  275 

Myelogenetic  fields  (areas)  of  Flechsig,  565 
Myelomeningocele,  618 
Myeloplaxes,  181 
Myelospongium,  486,  490 
Myoblasts,  303,  307 
Myocardium,  224,  311 
Myocoel  (coelom),  75,  372 
Myotomes,  167,  294 

alternation    of,    with    vertebras,    184, 

295 
change  of  direction  in  fibres  of,  295 

degeneration  of,  295 
differentiation  of,  295 
fusion  of,  295,  314 
longitudinal  splitting  of,  295,  314 


INDEX. 


659 


Myotomes,  migration  of,  295,  314 

practical  suggestions  for  study  of,  217, 

3r4 
tangential  splitting  of,  295,  314 

Nsevi  pigmentosi,  452 
Nail  groove,  446 
Nail  wall,  446 
Nails,  the,  446 

epitrichium  of,  447 

eponychium  of,  447 

lunula  of,  447 

migration  of,  446 

practical  suggestions  for  study  of,  453 

replacement  of,  447 
Nanocephaly,  617 
Nares,  outer,  590 

posterior,  590 
Nasal  bone,  198 

conchae,  590 

fossae,  144,  589 

pit,  152,  320,  589 

process,  lateral,  i  52 
medial,  152 

sacs,  589 

septum,  196,  320 
Naso-frontal  process,  151,  318 
Naso-optic  furrow,  146,  151,  589 
Navicular  bone,  204 
Neck,  development  of,  149 
Neck-rump  length  of  embryos,  157 
Neopallial   commissure    (see   also   Corpus 

callosum),  475 
Neopallium,  474,  475,  477,  559  to  567 

centrifugal  connection  (see  also 
Tracts,  pyramidal,  Cortico-pon- 
tile  fibers  and  Fibers  projection 
descending,)  478,  479,  553,  562, 

565 

centripetal  connections      (see      also 

Fillets,  Thalamic  radiations  and 

Fibers,  projection,     ascending) , 

477.  478.  544,  553,  562,  565 
Nephrogenic  tissue,  395 
Nephrostomes,  389 
Nephrotomes,  391 
Nereis,  cleavage  in,  48 
Nerve  fibers,  afferent  peripheral,  458,  493 

efferent  peripheral,  459 
Nerves,  cranial,  abducens,  VI,  469,  522 

nucleus  and  roots  of,  495,  522,  524, 

53  ! 
acoustic,    (auditory)   VIII,  469,  472, 

5°6,  5°7,  5*°,  525,  598 
cochlear  root,  507,  598 
cochlear  ganglion,  506,  598 

part,  469,  472 
vestibular  ganglion,  506,  598 

part,  469,  472 

vestibular  root,  507,  510,  525,  598 
facialis,  VII,  469,  471 
.  afferent   roots,  solitary  tract,   506, 

525 

chorda  tympani,  505 
efferent  nucleus  and  roots  of,  495, 

524 
geniculate  ganglion  of,  505,  598 


Nerves,  great  superficial  petrosal  branch, 

505 

glossopharyngeus,  IX,  469,  471 
afferent  part  of,  469 
afferent  roots,  506 
efferent  nucleus  and  efferent  root 

of,  495 

ganglion  of  the  trunk  (petrosum), 
502 

of  the  root,  502 
lingual  and  tympanic  banches  of, 

505 
hypoglossus,  XII,  469,  522 

nucleus  and  roots  of,  495,  531 
lateral  line,  469 
olfactory,  I,  474,  475,  508,  512 

terminal   nuclei,  or  mitral  cells  of 

the  olfactory  bulb,  512 
optic,  II,  461,  474,  512,  537,  586 

ganglion  cells  of,  512 
oculomotor,  III,  469 

nucleus  and  roots  of,  495 
somatic,  469  to  472 
spinal  accessory,  XI,  471,  502 
efferent  fibers  of,  503 

nuclei  and  roots  of,  495 
splanchnic,  467  to  472 
trigeminus,  V,  467,  469,  471 
afferent    root  (portio    major),    and 

spinal  V,  467,  508,  510,  525 
efferent  nuclei  and  roots  of,  495 
Gasserian  or  semilunar  ganglion, 

467,  507 

mandibular  branch,  507 
maxillary  branch,  507 
mesencephalic  root  of,  530 
opthalmic  branch,  507 
trochlear,  IV,  469 

nucleus  and  roots,  of,  495 
vagus,  X,  469,  471 
afferent  roots,  506 
efferent  fibres  of,  503 

nuclei  and  roots  of,  495,  524 
ganglia  of  root,  502 
ganglion  of  trunk  (nodosum),  502 
Nerves,  spinal,  peripheral,  dorsal  branch 

of,  494,  497 

ventral  branch,  494,  497 
Nervous  system,  the,  454 
anomalies  of,  567 
anterior  neuropore,  458 
brain,  460 

central     distinguished    from    peri- 
pheral, 456 

cerebrospinal  ganglia,  458 
components  of,   afferent  and  effer- 
ent, 454 

derivation  of,  458 
epichordal    segmental     brain     and 

nerves,  466 

general  considerations  of,  454,  455 
human,  496 
nerve  fibres,  458 
neural  crest,  458 
folds,  458 
groove,  458 
plate,  458 


660 


INDEX. 


Nervous  system,  neural  tube,  458 

practical  suggestions  for  study  of, 

568 

primitive  nervous  mechanism,  455 
root   fibers  of,   458 
spinal  cord  and  nerves,  460,  464 
two-neurone  reflex  arc,  455 
three-neurone  reflex  arc,  457 
vertebrate,  457 
central,  456 

suprasegmental  structures  of,  457, 

464 

human,  afferent  peripheral  and  sym- 
pathetic neurones,  496 
anomalies  of,  567 
cell   proliferation   of,    486 
cerebellum,  462,  464,  473,  519,  532 
corpora  quadrigemina,  474,  524,  537 
development  of  the  lower  (interseg- 
mental)    intermediate    neurones, 

5°9 

differentiation  of  peripheral  neu- 
rones of  cord  and  epichordal  seg- 
mental  brain,  493 

early  differentiation  of  nerve  ele- 
ments, 490 

epicordal  segmental  brain,  519 

epithelial  stage  of,  486 

further  differentiation  of  neural 
tube,  513 

general  development  of,  during  first 
month,  479 

histogenesis  of,  485 

spinal  cord,  513 
peripheral,  454 

effectors  of,  455 

receptors  of,  455 
sympathetic,  465 

efferent  peripheral  visceral  neurones 

of,  458 

vertebrate,  bilateral  character  of,  457 
cephalization,  457 
general  features  compared  with  hu- 
man, 464 

general  plan  of,  457 
segmentation  of,  457 
typical,  457 
Net  knots,  i 
Neural  crest,  79,  458,  497 

relation    to    cerebrospinal   ganglia, 

458 

segmentation  of,  458 

separation  of,  458 
folds,  73,  458,  479 

fusion  of,  458,  479 
groove,  73,  77,  78,  84,  89,  91,  139, 

458.  479 

plate,  81,  458,  479 

differentiation  of,  460 

tube,  74,  84,  458,  479 

alar  plate,  484,  519,  522,  526 
basal  plate,  484,  519,  521 
blood  vessels  of,  515 
cells  of,  486,  488,  490,  491 
cervical  flexure,  485 
defects  in  the  region  of,   619 
floor  plate  of,  460,  480 


Neural  crest,  further  differentiation  of,  513 
lateral  plates  of,  460,  480 
layers  of,  486,  492,  521 
methods  of  study  of,  568 
limiting  membranes  of,  486 
neuromeres,  463,  484 
order  of  development  of,  485,  513, 

^522,   526,   549 

origin  of  malformations  of,  619 
roof  plate  of,  460,  480,  520 
sulcus  limitans,  484,  519 
Neurenteric  canal,  74,  318 
Neurilemma,  485,  499 

cells  of,  499 

Neuroblasts  of  His,  492 
Neuro-epithelium,  591,  596 
Neurofibrils,  485,  491,  496 
Neuroglia  cells,  488,  492 

fibers,  490 

Neuromeres,  463,  484 
Neurone  layer,  see  Mantle  layer 
Neurones,   afferent   peripheral,   454,    464, 

496  to  509 

afferent  versus  efferent,  464 
association,  464,  475,    535,    537,    565 
central,  456 
differentiation  of,  485 
distal  (first)  optic,  583 
efferent  peripheral,  454,  464,  493   to 

496 
intermediate,  456,  466,  509 

intersegmental     (see     also    Ground 
bundles  and  Formatio  reticularis) , 
466,  472,  485,  509  to  513,  522 
of  epichordal  segmental  brain,  472 
to  suprasegmental  structures,  466 
intersegmental,    of   epichordal  brain, 

522  to  525 

middle  (second)  optic,  583 
somatic  efferent,  466 
splanchnic  efferent,  466 
suprasegmental,  485 
Neuropore,  74 

anterior,  458,  480 
Nipple,  the,  450 
Nodule  of  cerebellum,  533 
Normal  embryos,  158 
Normoblasts,  272,  273,  274 
Nose,  457,  464,  512,  589 
anomalies  of,  216,  620 
bucco-nasal  membrane,  590 
Jacobson's  organ,  591 
nasal  conchas,  590 
origin  of,  148,  589 

practical  suggestions  for  study  of,  603 
primitive  choanen,  590 

palate,  590 
sinuses  of,  590 
Notochord,  72,  182 
Nuck,  diverticulum  of,  426 
Nuclear  groups,  127 

layer  of  neural  tube,  486 
membrane  of  typical  cell,  i 
reticulum  of  typical  cell,  i 
Nuclei,  lateral,  473 

of  columns  of  Burdach,  466,  473,  478, 

527 

of  columns  of  Goll,  466,  473,  478,  527 
of  thalamus,  544 


INDEX. 


661 


Nuclei,  pontile,  473,  526,  537 

receptive,  474 

red  (ruber),  473,  524 

terminal    of    afferent    nerves    of   epi- 

chordal  brain,  525  to  532 
of  tractus  solitarius,  469,  526,  531 
of  V,  467,  527.  53°.  S31 
of  VIII,  469,  529 

tracts  from  Deiter's,  473,  518 
Nucleoli,  function  of,  2 

false,  i 

true,  2 

Nucleoplasm,  i 
Nucleus,  the,  i 

ambiguous,  X,  495,  524 

caudatus  of  corpus  striatum,  553 

commissuralis,  526 

dentatus,  478,  479,  537 

diffuse,  2 

dorsal  efferent,  X,  495 

functions  of,  2 

habenulae,  462,  540 

incertus,  531 

inferior  olivary,  473,  526,  527,  531 

intercalatus,  531 

lateral,  527 

lenticularis,  553 

lentiformis,  553 

of  Darkschewitsch,  524 

sperm,  37 

structure  of,  i 
Nutrition  of  earliest  stages  of  embryo,  108 

Obex,  520 

Obturator  foramen,  207 
Occipital  bone,  194,  196 
Occipital  depression,  146 
Occulomotor,  III,  nerve,  469 
Odontoblasts,  326 
Odontoid  process  (dens),  188 
CEsophageal  region,  318 
(Esophagus,  the,  336 

anomalies  of,  357 

methods  of  study  of,  3  59 
Olfactory  apparatus,  see  Nose 

area  (see  also  Arc  hi  pallium),  565 

bulbs,  459,  548 

lobes,  476,  485,  547,   548 

anterior,  476,  546,  547,  548,  589 
posterior,  476,  546,  547,  548,  589 

I,  nerve,  4^4,  475,  508,  512 

peduncle,  548 

placodes,  589 

stalk,  548 

tracts,  474,  475,  512,  544 
Olives,  accessory,  527 

inferior,   473,    526,    527,    531 

superior,     530 

Olivo-cerebellar  fibers,  528,  536 
Omenta,  anomalies  of,  384 
Omental  bursa,  380 

epiploic  foramen  of,  380 
Omentum,  379 

greater,  380 

lesser,  381 
Omosternum,  215 
Omphalocele,  622 
Omphalomesenteric  arteries,  105,  107,239 


Omphalomesenteric  veins,  106,  238 
Oocyte,  primary,  10,  n,  20 

secondary,  21 

Opercula  of  insula,  559    560 
Optic  apparatus,  see  Eye 

chiasma,  512,  538 

CUP,  576,  579,  587 

depression,  573 

evagination,  574,  586 

lobes,  462,  474,  475 

II,  nerve,  461,  474,  512,  537,  586 

neurone,  first  or  distal,  583 
second  or  middle,  583 

radiation,  477,  478 

stalk,  574,  586 

thalami,  586 

tract,  475,  512,  537,  586 

vesicles,  144,  461,  481,  574 

vesicle  area,  574 
Ora  serrata,  580 
Orange  G,  636 
Oral  fossa,  143,  151 

pit,  319 

Orbitosphenoid  bone,  195 
Organ  of  Corti,  467,  474,  565,  597 

of  Giraldes,  421 

of  Rosenmiiller,  419 
Organogenesis,  163 
Origin  of  the  aorta  from  both  ventricles, 

286 

Orth's  fluid,  632 
Os  calcis  (calcaneus),  208 

centrale,  217 

coxae,  207 

Ossa  suprasternalia,  189 
Osseous  tissue,  173 
Ossification  center,  175,  178 

endochondral,  176 

intracartilaginous,  176 

intramembranous,  173 

subperiosteal,  176,  178 

stage,  1 86 

Osteoblasts,  175,  275 
Osteoclasts,  175,  275 
Osteogenetic  tissue,  175,  177 
Ostium  abdominale  tubae,  418 

atrio-ventriculare,  232 
Otic  ganglion,  508 
Otocyst,  592 
Ova,  alecithal,  12,  42,  43 

centrolecithal,  12,  42,  45 

primitive,  411 
number  of,  413 

telolecithal,  12,  42,  44,  46 
Ovarian  cysts,  614 

(Graafian)  follicle,  412 
liquor  folliculi,  412 
rupture  of,  413 
stratum  granulosum  of,  412 

zona  pellucida,  412 

radiata,  412 

Ovarian  ligament,  the,  426 
Ovary,  the,  409 

anomalies  of,  437 

corpus  haemorrhagicum,  414 
luteum,  413 

descent  of,  426,  441 


662 


INDEX. 


Ovary,  diverticulum  of  Nuck,  426 

egg  nests,  411 

ligaments  of,  426 

medullary  cords  of,  409,  410 

migration  of,  421,  426 

Miillerian  duct  of,  417 

parasitic  growths  of,  613 

Pfliiger's  egg  cords  of,  411 

practical  suggestions  for  study  of,  441 

primary  Graafian  follicle  of,  411 

rete  of,  410 

stratum  germinativum,  410 

theca  folliculi,  412 
Oviduct,  418 

anomalies  of,  437 

fimbriag,  418 

non-stalked  hydatid  of  Morgagni,  418 

ostium  abdominale  tubas  of,  418 
Ovists,  XIII 
Ovulation,  30 
Ovum,  the,  10,  412 

Bryce  and  Teachers,  90,  94,  96 

containing     two     originally     distinct 
anlagen,  6 1 1 

faulty  implantation  of,  627 

fertilization  of,  35 
of  human, 

fixation  to  uterus,  120 

Graf  Spec's,  90,  i  58 

Leopold's,  89,  158 

Peters',  90,  158 

size  of,  10 

Palate,  the,  320 

bone,  198 

cleft,  216,  620,  621, 

primitive,  590 
Palatine  processes,  320 
Pallium,  462,  474,  481,  545,  546,  548  to  567 

archipallium,     475,      512,     544,     548, 
553  to  559 

association  neurones  of,  475,  535,  537, 

565 

calcarine    area    or    region      (see    also 
Visual  area),  564,  565 

corpora  striata,  462,  474,  548 

cortex  of,  561 

development  of,  475 

hemispheres  of,   464,   477,   481,    545, 
548  to  567 

layer  of  giant  pyramid  cells,  565 

layers  of,  564 

neopallium,  457,  559  to  567 

postcentral  area  of,  478,  562,  564,  565 

precentral  area  of,  479,  564,  565 

rhinencephalon,  462,  474,  547 
Pancreas,  the,  351 

anomalies  of,  3  59 

cells  of,  355 

connective  tissue  of,  3  53 

duct  of  Santorini  of,  352,  359 
of  Wirsung  of,  352,  359 

histogenesis  of,  3  54 

islands  of  Langerhans,  355 

practical  suggestions  for  study  of,  360 
Pander,  XIII 
Papillae,  lingual,  322 

filiform,  322 

fungiform,  322 


Papillae,  hair,  447 

nerve,  445 

renal,  396,  401 

vascular,  445 
Papillares  muscle,  232 
Paradidymis,  the,  421 
Paraffin  embedding,  634 

sections,  634 

fixing  to  slide,  63  5 

mounting  of,  63  5 

staining    with     haematoxylin    and 

eosin,  636  • 
Paraphysis,  461,  541 
Paraplasm,  i 
Parasitic  duplicity,  612 

origin  of,  614 
Parasitic  structures  in  the  sexual  glands, 

613 

Parathyreoids,  333 
Parietal  bones,  198 

cavity,  222 
of  His,  374 

mesoderm,  75,  87,  138,  372 

recess,  dorsal,  of  His,  374 
Parolfactory  area  of  G.  Elliot  Smith,  (see 

also  Preterminal  area),  476,  548 
Paroophoron,  the,  420 
Parovarium,  the,  419 
Pars  basilaris,  194 

ciliaris  retinae,  587 

cystica,  346 

hepatica,  346 

mastoidea,  195 

optica  retinae,  587 

petrosa,  195 

squamosa,  194 

subthalamica,  see  Hypothalamus 
Partes  laterales,  194 
Patella,  the,  208 
Pathological  embryos,  i  58 
Paton,  concerning  development  of   pyra- 
mids, 562 

concerning  peripheral  nerves,  501 
Peduncles  of  cerebellum,  middle,  473,  478, 
480,  530,  537 

inferior  cerebellar,  see  Restiform  body 

superior,  473,  478,  480,  537 
Pellicle  of  cytoplasm,  172 
Pelvic  girdle,  207 
Penis,  the,  428 

supernumerary,  613 
Perenyi's  fluid,  633 
Perforated  space,  posterior,  540 
Perforatorium,  14 
Pericardia!  cavity,  primitive,  88 

method  of  study  of,  385 
Pericardium,  the,  372,  379 

anomalies  of,  384 
Perichondrium,  177 
Periderm,  the,  444 
Perilymph,  596 
Perilymphatic  space,  596 
Perimysium,  311 
Perineal  body,  the,  428 
Perobrachius,  623 
Perichordal  sheath, 
Periosteal  buds,  177 
Periosteum,  175 


INDEX. 


663 


Periotic  capsule,  193 

Peripheral  nervous,    system,    see   Nervous 

system,  peripheral 
Peristomal  mesoderm,  58,  77 
Peritoneum,  384 
Peritonsillar  fissure,  533 
Perivitelline  space,  1 1 
Permanent  teeth,  328 
^eromelus,  623 
Peropus,  623 

Persistence  of  the  cloaca,  3  58 
Pes  pedunculi,  473,  478,  530,  531,  565 
Peter,  concerning  nasal  sac,  589,  590 

concerning   origin   of   endolymphatic 

appendage  in  Amphibia,  593 
Peters'  ovum,  90,  115,  139,  241 
Peyer's  patches,  345 
Pfliiger's  egg  cords,  411 
Phaeochrome  cells,  430 

granules,  430 
Phaeochromoblasts,  431 
Phalanges,  205 
Pharyngeal  membrane,  319,  331 

region,  318 

tonsils,  331 

Pharyngopalatine  arch,  331 
Pharynx,  the,  330 

anomalies  of,  357 

development  of,  330 

glossopalatine  arch,  331 

pharyngopalatine  arch,  331 

pillars  of  the  fauces,  331 

practical  suggestions  for  study  of, 

359 

Physico-chemical  theory  of  monsters,  625 
Picric  acid  and  acid  fuchsin,  636 
Picro-acid  fuchsin,  636 
Piersol,  classification  of  malformations  of 

the  extremities,  622 
Pig  embryos,  technic  for,   630 
Pigment,  445 

of  neurones,  485,  496 
Pillars  of  the  fauces,  331 
Pineal  body,  461,  474,  540 

stalk,  540 
Pisiform,  205 

Pituitary  body,   irregular  tumors  of,   612 
Placenta,  114 

anomalies  of,  134 

annular,  134 

attachment  of,  to  ovum  and  to  uter- 
ine wall,  132 

blood  vessels  of,  131,  243 

bipartita,  134 

chorion  frondosum,  122,  124 

decidua  basalis,  122,  124 

discoidal,  114 

duplex,  135 

expulsion  of,  134 

fcetalis,  114 

functions  of,  128 

maternal,  114 

membranacea,  134 

practical  suggestions  for  study  of,  135 

prasvia,  132 

relations  of,  to  uterine  mucosa,   114, 
124 


Placenta,  size  of,  132 

spuria,  135 

succenturiata,  135 

uterina,  114 

zonular,  114 
Placentas,  multiple,  114 
Placental  septa,  127 
Placentalia,  114 
Placodes,  459,  502,  512 

auditory,  592 

epibranchial,  459 

olfactory,  589 

suprabranchial,  459 
Plagiocephaly,  216 
Plasmodi-trophoderm,  121,  125,  126 
Plasmosomes,  2 
Plastic  reconstruction,  638 
Plastids,  2 
Plexus,  Auerbach's,  498 

chorioideus,  see   Chorioid  plexus 

Meissner's,  498 
Pleura,  the,  368,  379 
Pleural  cavities,  375 
Pleuroperitoneal  membranes,  377 
Pleuroperitoneum,  372 
Plica  arcuata,  555 

chorioidea  (fold),  554 

encephali  ventralis,  460 

rhombo-mesencephalica,  482 

semilunaris,  589 
Plicae  palmatas,  419 
Polar  bodies,  17,  18,  20 

differentiation,  12 

relation  to  production  of  monsters, 

6i5 

rays,  6 

Polydactyly,  217,  623 
Polymorphonuclear  leucocytes,  275 
Polynuclear  leucocytes,  275 
Polysomatous  monsters,  625 
Polyspermy,  39 
Pons  varolii,  482,  530 
Pontile  nuclei,   473,    526,    530,    537 
Pontine  flexure,  484 
Porencephaly,  617 
Portio  major,  508 

Postbranchial  branches  of  nerves,  471 
Posterior   arcuate  fissure,  555 

colliculi,  see  Posterior  corpora  quadri- 
gemina 

corpora  quadrigemina,  474,  524,  537 

horn  (dorsal  gray  column)  ,515 

longitudinal  fasciculus,  see  Fasciculus, 
medial   longitudinal 

nares,  321 

Prebranchial  branches  of  nerves,  471 
Precervical  sinus,  147,  151 
Preformation  theory,  XIII 
Preformationists,  XIII 
Pregnancy,  abdominal,  31 

mammary  gland,   during,  450 

proof  of,  128 

tubal,  3  r 

Premolar  teeth,  328 
Premuscle  tissue,  296 
Premuscle  sheath,  305 
Preoptic  recess,  538 


664 


INDEX. 


Prepuce,  in  the  female,  428 

in  the  male,  428 
Preservation  of  tissues,  633 
Presphenoid  bone,  195 
Preterminal  area  of  G.  Elliot  Smith,  476, 

548 

Primary  areas  or  fields    of   Flechsig,    565 
Primary    germ    layers,    (see    also    Germ 

layers},  55 

Primary  oocyte,  10,  n,  20 
Primitive  body  cavity  (ccelom),  75 

coordinating  mechanism,  511 

entoderm,  137 

groove,  65,  90 

gut  (see  also  Archenteron) ,  55,  76,  317, 

372 
practical  suggestions  for  study  of, 

359,  385 
intestinal  cord,  in  the  chick,  66,  81 

in  Mammals,  70 

in  Reptiles,  67 
organs,  56 
pericardial  cavity,  88,  222,  311,373 

practical  suggestions  for  study  of, 

385 

segments,  72,  143,  293,  300 

practical     suggestions    for   further 
study  of,  183 

streak,  in  the  chick,  65 

in  Mammals,  69 
Primordial  cranium,  193 
Proamnion,  84,  108 
Processus  neuroporicus,  461 

reticularis,  518,  523 

vaginalis  peritonei,  424 
Procuring  and  handling  material,  629 

amphibian  embryos,  629 

chick  embryos,  630 

frog's  eggs,  629 

human  embryos,  159,  631 

mammalian  embryos,  630 

pig  embryos,  630 

rabbit  embryos,  63 1 

Production    of    duplicate    (polysomatous) 
monsters,  625 

of  monsters  in  single  embryos,  626 
Progamous  determination  of  sex,  415 
Projection  fields,  565 
Proliferation  islands,  127 
Pronephric  duct,  387,  388 
Pronephros,  the,  387 

practical  suggestions  for  study  of ,  439 

pronephric  duct  of,  387 
tubules  of,  388 

significance  of,  388 
Pronucleus,  female,  18,  35 

male,  20,  35 
Prophase,  4 
Prosencephalon  (fore-brain),  461,  464,  474 

diencephalon,  462,  474 

peripheral  neurones  of,  508 

telencephalon,  462,  474 
Prosopopagus  parasiticus,  612 
Prostate  gland,  405 
Prot  entoderm,  58 

of  Amphibians,  58,  60 

of  Birds,  64 


Protentoderm  of  Mammals,  70 

of  Reptiles,  63 
Protoplasm,  structure  of,  i 
Protozoa,  cell-division  in,  4 

conjugation  in,  40 
Psalterium,  see  Fornix  commissure 
Pterygoid  hamulus,  195 

process,  195,  198 
Pubis,  the,  207 
Pulmonary  artery,  231 
Pulp  of  teeth,  326,  327 
Pulpy  nuclei,  183 
Pulvinar  thalami,  540 
Purkinje  cells,  534,  536 
Pygopagus,  608 

Pyramids    (see    also    Tracts,    pyramidal), 
479,  528,  530,  531 

Quadrigemina,  anterior,  see  Anterior  cor- 
pora quadrigemina. 

posterior,  see  Posterior  corpora  quad- 
rigemina 

Rabbit,  formation  of  amnion  of,  108 

embryos,  technic  for,  631 
Rabl,  concerning  origin  of  vitreous,  585 

concerning  sex  cells,  407 
Rachischisis,  313,  617,  619 

cystica,  617 
Radius,  204 
Ramus,  200 

communicans,  gray,  499 

white,  494,  499 

Ranvier,  concerning  the  origin  of  connec- 
tive tissue  fibers,  170 

Raphe   (of  epichordal  segmental     brain), 
522 

(of  scrotum),  430 
Rathke's  pocket,  320 

pouch,  538 
Receptors,  455,  458,  464,  467,  469 

visual,   508,   512 
Recessus  postopticus,  461,  538 

praeopticus,  461,  538 
Recklinghausen,  von,  concerning  deficient 

growth  of  blastoderm,  619 
Reconstruction,  637 

graphic,  637 

plastic  or  wax,  638 
Rectum,  the,  342,  403 
Red  blood  cells,  272,  273 
Reduction,  Minot's  view  of,  29 

of  chromosomes  (see  also M aturation) , 

*7,  4i3 
practical    suggestions    for   study    of, 

33,  34 

theoretical  aspects  of,  28 

Weismann's  theory  of,  29 

with  tetrad  formation,  27 

without  tetrad  formation,  28 
Reflex  arc,  513 

two-neurone,  455 

three-neurone,  456 
Regnier  de  Graaf,  XIII 
Reichert,  XIV 
Rejuvenescence  theory,  40 
Remak,  views  of  cell-division,  4 


INDEX. 


665 


Renal  corpuscle,  400 
papihse,  396 
pelvis,  primitive,  394 
portal  system,  259,  393 
pyramids,  400 
tubules,  convoluted,  396 

straight,  394,  395 
Respiratory  system,  the,  362 
anomalies  of,  370 
larynx,  363 
lungs,  366 

practical  suggestions  for  study  of,  370 
trachea,  365 

Restiform  body,  473,  528 
Rete  cords,  407 
ovarii,  410 
testis,  414,  415 
Retention  cysts,  622 
Reticular  formation,  472,  478,  522  to  525 

gray,  523 
_  white,  523 

tissue,  origin  of  fibers  of,   171 
Retina,  461,  508,  512,  580 
amacrine  cells  of,  582 
area  centralis,  582 
bipolar  cells  of,  512,  583 
cone  bipolars,  584 
defective  pigmentation  of,  452 
differentiation  of  cells  of  nuclear  layer, 

582 

distal  (first)  optic  neurone,  583 
fovea  centralis,  582 
layer  of  ganglion  cells  of,   581 

of  nerve  fibers  of,  581 
macula  lutea,  582 
middle  (second)  optic  neurone,  583 
Miiller's  or  sustentacular  cells,  582 
nervous  part,  580 
non-nervous  part,  580 
ora  serrata,  580 
pigmented  layer,  580 
primitive  nuclear  layer  of,  581 
rod  and  cone  cells  of,  582,  583 

bipolars,  584 
Retterer,  concerning   lymphatic  tissue  of 

tonsils,  331 
Rhinencephalon,    462,  474,   512,   544,   547 

to  548 
Rhombencephalon  (rhombic   brain),  461, 

482,  502 
Rhombic   brain    (rhombencephalon),  461, 

482 

cerebellum,  462 
tela  chorioidea,  462 
grooves,  496 

!ip,  52°,  526,  S32 

Rhombo-mesencephalic  fold,  461,  482 
Rhythmical  contractions,  102,  116 
Ribbons  of  sections,  634 
Ribs,  the  188 

capitulum  of,  189 

costo- vertebral  ligaments  of,  188 

foramen  transversarium,  189 

ossification  of,  189 

tuberculum  of,  189 
Rods,  508,  512,  582,  583 
Rolando,  fissure  of,  561 


Rolando,  substantia  gelatinosa  of,  527 

tuberculum  of,  531 
Roof   plate    (dorsal    median   plate),    460, 

480,  520 
Root  fibres,  afferent,  458 

sheath,  the,  447 
Rosenberg's  theory  concerning  vertebrae, 

214 

Rosenmiiller,  organ  of,  419 
Rotation  of  extremities,  155 
Roux,     concerning     source     of     parasitic 

growths,  616 

Rubro-spinal  tract,  473,  518 
Rupture  of  the  membranes,  117 

Sabin,     concerning    origin    of    lymphatic 

vessels,  277 
Saccule,  596 
Sacral  flexure,  144 

Sala,  concerning  origin  of  lymphatic  ves- 
sels, 276 
Salivary  glands,  the,  328 

crescents  of  Gianuzzi,  330 

histogenesis  of,  329 

sublingual,  328 

submaxillary,  328 
Santorini,  duct  of,  352 
Sarcoplasm,  309 
Scala  media,  596 

tympani,  596,  597 

vestibuli,  596,  597 

Schaper,  concerning  development  of  cere- 
bellum, 534 
Scaphocephaly,  216 
Scapula,  203 
Schleiden,  XIV 

Schmidt,  concerning  mammary  gland,  449 
Schultz,    concerning   potentiality   of  germ 

cells,  616 
Schwann,  XIV 
Sclera,  585 

Sclerotome,  167,  183,  293,  307 
Scrotum,  the,  424,  430 
Sea-urchin  eggs,  method  for  study  of,  15, 

53 

Sebaceous  glands,  the,  449 
Secondary  oocyte,  21 
Secretory  function,  330 
Section  cutting,  634 

celloidin  sections,  634 

paraffin  sections,  634 

serial  sections,  634 
Segmentation  cavity,  50 
Segmentation  cells,    development    of   iso- 
lated group  of,  to  form  monsters, 

615 
Segmental  part  of  epichordal  brain,  464, 

466 

Segmentation  (see  also  Cleavage),  42 
Segments,  primitive,  72,  143,  165,  293,  300 
primitive,   method  of  study  of,   218, 

3J4 

of  segmental  brain  and  cord,  512,  513 
Semilunar  ganglion,  467 
Seminal  filament  or  spermatozoon,  10,  13 

vesicles,  420 
Seminiferous  tubules,  414 


666 


INDEX. 


Sense  organs,  special,  573 

anomalies  of,  601 

ear,  592 

eye,  573 

nose,  589 

practical  suggestions  for  study  of,  602 
Septa,  the,  229 

anomalies  of,  285 
Septal  marginal  layer,  521 
Septum  aorticum,  230 

atriorum,  229 

medulla?,  521 

pellucidum,  476,  559 

spurium,  231 

superius,  229 

transversum    (see    also    Diaphragm), 

374,  376,  379 
practical    suggestions  for  study  of, 

3.85 

ventriculorum,  229 
Serial  sections,  634 
Serosa,  107 
Sertoli,  cells  of,  2 1 
Sex  cells,  407 
cords,  408 

determination  of,  415 
Sexual  elements,  10,  407 
Sheaths,    myelin    (medullary),  485,  501 

neurilemma,  485 
Sherrington,      concerning     effectors     and 

receptors,  455 
Shoulder  girdle,  203 
Siamese  twins,  609 
Sigmoid  colon,  341 
mesocolon,  383 
Sinus,  cavernous,  254 
confluence  of,  255 
coronarius,  231,  256 
frontal,  590 
maxillary,  590 
petrosal,  2  54 
sagittal,  254,  255 
sphenoidal,  590 
terminalis,  237 
transverse,  2  54 
venosus,  227,  231 
Sinusoids,  259,  263,  347,  348 
Sinusoidal  circulation,  348 
Situs  viscerum  in  versus,  355 
Skeletal    musculature,    see     Musculature, 

skeletal 

system,  anomalies  of,  213 
appendicular  skeleton,  202 
axial  skeleton,  182 
development  of  the,  165 

of  joints,  209 
head  skeleton,  190 
notochord,  182 
practical  suggestions  for  study  of, 

217 

ribs,  1 88 
sternum,  189 
vertebrae,  183 
Skeleton,  axial  (see   also   Axial  skeleton}, 

182 

appendicular  (see   also  Appendicular 
skeleton),  202 


Skin,  the,  444 

anomalies  of,  451 

dermis,  445 

epidermis,  444 

glands  of,  449 

pigment  of,  445 

practical  suggestions  for  study  of,  453 
Skull,  defects  of,  616 

development  of,  190 
Smegma  embryonum,  449 
Smith,  G.  Elliott,  concerning  archipallium, 

476 
Smooth  muscle,  311 

histogenesis  of,  312 
Sobotta,    concerning    maturation    in   the 

mouse,  21 
Sole  plate,  446 

Somaesthetic  area  of  pallium,  477,  564,  565 
Somatic  area  (see  also  Pallium,  precentral 
area),  565 

segmentation,  457,  467 

structures,  465 
Somatochrome  cells,  496 
Somatopleure,  75,  109,  372 
Somites,  mesodermic,  72 
Spencer     and     Darwin,    concerning   ferti- 
lization, 40 
Sperm  nucleus,  34,  37 

method  for  study  of,  41 
Spermatids,  21 
Spermatocytes,  21 

primary,  24 

secondary,  24 
Spermatogenic  cells,  2 1 
Spermatogenesis,  21 
Spermatogonia,  21,  414 
Spermatozoon,  the,  13 

diagram  of,  14 

discovery  of,  XIII 

practical  suggestions  for  the  study  of, 

significance  of,  i  5 
flagellate,  13 
Sphenoid  bone,  195,  197 
Sphenomandibular  ligament,  200 
Sphenopagus,  612 
Sphenopalatine  ganglion,  508 
Spigelius,  lobe  of,  3  50 
Spina  bifida,  617,  618,  619 
cystica,  617 
occulta,  618 

Spinal  accessory,  XI,  nerve,  471,  502 
Spinal  cord,  the,  460,  464,  480,  513 
Clarke's  column,  473,  518 
dorsal  funiculi,  497,  510,  514 
gray  column,  465,  515 
septum  of,  517 
growth  of,  519 
ventral  funiculi,  514 
gray  column,  465 
lack  of,  618 
malformations  of,  617 
ventro-lateral  funiculus,  514 
ganglion,  497,  498 

cells,  unipolarization  of,  498 
meningocele,  618 
V,  467,  5°8.  525 


INDEX. 


667 


Spindle,  achromatic,  4 

central,  4 

Spino-cerebellar  tracts,  473,  478,  519 
Spiral  fibers  of  spermatozoon,  14 

filament,  25 

lamina,  597 
Spireme,  closed,  5 

open,  5 

thread,  5 

segmentation  of,  19 
Splanchnic  mesoderm,  106,  343 

or  visceral  structures,  465 
Splanchnoccel,  75 
Splanchnopleure,  75,  109,  372 
Spleen,  the,  282 

cavernous  veins  of,  282,  284 

haematopoietic  function  of,  272,  284 

pulp  cords  of,  282,  284 

splenic  corpuscles  of,  282,  284 

cells,  284 

Splenic  corpuscles,  282 
Spongioblasts,  486,  490 
Spongioplasm,  i 
Spongy  bone,  175 
Spuler,  concerning  the  origin  of  connective 

tissue  fibers,  170 

Staining     celloidin    sections   with    hzema- 
toxylin  and  eosin,  636 

differential,  63  5 

in  toto,  635 

nerve  tissue,  568  to  571 

paraffin    sections   with    hasmatoxylin 
and  eosin,  636 

with  Heidenhain's  hacmatoxylin,  637 
Stapes,  201,  599 

Starfish  eggs,  method  for  study  of,  15,  53 
Sternopagus,  609 
Sternum,  the,  189 

corpus  sterni,  190 

malformations  of,  609 

manubrium  sterni,  190 

ossification  of,  190 

xyphoid  process  of,  190 

cleft,  215 
St.     Hilaire,     concerning     malformations, 

605 

Stockard,  on  production  of  monsters,  626 
Stomach,  the,  336 

anomelies  of,  3  58 

rotation  of,  337 

practical  suggestions  for  study  of,  359 

region.  318 
Strahl,   concerning  the   mammary  gland, 

449 
Stratum  granulosum,  412 

cells  of,  413 
Streeter,   concerning    the    acoustic  nerve, 

599 

concerning  atrium  of  inner  ear,    593 
concerning    development    of    IX,  X, 

XI  cranial  nerves,  502,  503 
concerning  floor  of  fourth  ventricle, 

S31 
concerning   origin   of   endolymphatic 

appendage  in  man,  593 
concerning  origin  of  genu  facialis,  524 
concerning  rhombic  grooves,  496 


Stria  medullaris,  540,  545 

semicircularis,  550 

terminalis,  550,  555 
Striae  Lancisi,  558 
Striated  involuntary  muscle  tissue,  311 

voluntary     muscle    tissue,     cells    of, 

3°7 

endomysium  of,  311 

epimysium  of,  311 

fibers  of,  308 

histogenesis  of,  307 

intermuscular  tissue  of,  311 

perimysium  of,  311 

practical  suggestions  for  study  of, 

315 

sarcoplasm,  309 
Stylohyoid  ligament,  201 
Styloid  process,  196,  201 
Subclavian  artery,  245 
Sublingual  gland,  329 
Submaxillary  ganglion,  508 

gland,  328 

Subperiosteal  ossification,  176,  178 
Substantia  gelatinosa  of  Rolando,  527 

propria  corneas,  588 
Sudoriferous  glands,  the,  449 
Sulcus  hypothalamicus,  538 
limitans,  484,  519,  531 
longitudinalis,  229 
Monroi,  538 
Superior  peduncle  of  cerebellum,  473,  478, 

480,    537 

Suprasegmental  structures  of  Adolf  Meyer, 
(see  also  Cerebellum,  Mid-brain 
roof,  Corpora  quadrigemina  and 
Pallium)  457,  464,  473,  474,  512, 

5i3 

characteristics  of,  464 

connections  of  see  Cerebellum,  Mid- 
brain  roof , Corpora  quadrigemina, 
Archipallium  and  Neopallium 

tracts  to  (see  also  Cerebellum,  Mid- 
brain  roof  Corpora  quadrigemina, 
Archipallium  and  Neopallium). 

473.478,  5l8, 

Supplemental  cleavage,  64 
Supracondyloid  process,  216 
Supraglenoidal  tuberosity,  203 
Supraoccipital  bone,  194 
Suprarenal  glands,  430 

chromaffin  cells,  430 

cortical  substance  of,  431 

lipoid  granules  of,  430 

medullary  substance  of,  431    ' 

organs,  432 

phaeochrome  cells  of,  430 

relation  to  kidney,  432 
Suprasternal  bones,  189,  215 
Sylvii,  fossa  of,    546,    547,    559 
Symblepharon,  620 
Symmetrical  duplicity,  606 

anterior  union,  610 

complete  duplicity,  605,  606 

middle  union,  609 

multiplicity,  61 1 

origin  of,  61 1 

posterior  union,  608 


668 


INDEX. 


Sympathetic  (autonomic)  system,  465 

nervous  system,  see  Nervous  system, 

sympathetic 
Sympathoblasts,  431 
Symphysis  of  lower  jaws,  319 
Sympus  apus,  623 

dipus,  623 

monopus,  623 

symelus  siren,  623 
Synapta,  cleavage  in,  43 
Synart hrosis,  210 
Syncephalus,  610 
Synchondrosis,  210 
Syncytial  layer,  125 
Syncytium  of  heart  muscle,  312 
Syndesmosis,  210 

Syngamous   determination   of  sex,   415 
Synophthalmia,  620 
Synosteosis,  215 
Synotia,  601,  6ro 
Synotus,  620,  621 
Synovia!  fluid,  211 
Syringomyelocele,  618 

Tactile    corpuscles   of    Meissner,    445 
Taenia  fimbriae,  555 

of  cerebellum,  532 
of  cerebral  hemispheres,  549 
of  medulla,  520 

Tail,  gradual  shortening  of,   144,   148,149 
Talus,  208 

Tarsus,  bones  of  the,  208 
Taste  buds  (see  also  Gustatory  system),  4  57, 

467. 

Tautomeric  column  cells,  510 
Teeth,  the,  323 

dental  groove,  324 
papilla,  324 
shelf,  324 

dentinal  canals,  327 
fibers  of,  327 
pulp  of,  326 
dentine,  324,  326,  327 
enamel,  325 
organ,  324 

membrana  preformativa,  326 
methods  for  study  of,  3  59 
milk,  324 
odontoblasts,  326 
permanent,  327 
true  molars,  327 
Tegmental  swelling,  524,  542 
Tegmentum,  531,  545 
Tela  chorioidea,  462,  540 
Telencephalon   (end-brain),   88,   462,  474, 

545  to  568 
corp. is    striatum,  462,  474,  481,  485, 

546 

pallium,  462,  474,  481,   545,   546 
rhinencephalon,   462,   474,    512,    544, 

547  to  548 
Telolecithal  eggs  (ova),  42,  44,  46 

method  for  study  of,  16,  53 
Telophase,  6 
Temporal  bone,  195,  197 

lobe,  549 
Tendons,  origin  of  fibers  of,  171 


Teratogenesis,  605 

causes  underlying  origin  of  monsters, 
624 

malformations   involving   more   than 
one  individual,  605 

malformations    involving    one    indi- 
vidual, 616 

Teratoid  tumors,  436,  437 
Teratomata,  616 
Terminal  arborizations,  494,  511 
Terminal  areas  of  Flechsig,  566 
Testicle,  the,  414 

anomalies  of,  436 

cells  of,  21,  415 

descent  of,  423,  441 

mediastinum  testis,  415 

migration  of,  422,  426 

practical    suggestions    for    study    of, 
441 

processus  vaginalis  peritonei,  424 

rete  testis,  414,  415 

seminiferous  tubules,  convoluted,  414 
straight,  414 

stroma  of,  415 

tunica  albuginea  of,  408,  414 

vaginalis  propria,  426 
Testis,  mediastinum,  415 

parasitic  growths  of,  614 

rete,  414,  415 
Tetrabrachius,  609 
Tetrads,  1 7 

origin  of,  19 
Thalamic  radiations,  477,   478,    544,    552, 

553>  S^1 

Thalamus,  474,  485,  512,  543,  553 
Theca  folliculi,  30,  32,  412 
Theoria  generationis,  XIII 
Thigh,  development  of,  i  54 
Thoracic  region,  defects  of,  622 
Thoracogastroschisis,  622 
Thoracopagus,  609 

parasiticus,  609 
Thoracoschisis,  384 
Thymus  gland,  285,  334 

anomalies  of,  357 

atrophy  of,  335 

histogenesis  of,  335 

malformations  of,  609 

tumors  of,  613 
Thyreoglossal  duct,  333 
Thyreoid  gland,  332 

anomalies  of,  357 

colloid  secretion  of,  332 

epithelial  bodies,  333 

its  relation  to  formation  of  blood  cells, 

275,  336 

parathyreoids,  333 

thyreoglossal  duct  of,  333 
Thyreoids,  lateral,  333 

theories  concerning,  333 
Thyng,  concerning  anomalies  of  pancreas, 

359 

Tibia,  208 

Tissues,  adenoid,  332 

adipose,  171 

chromaffin,  433 

connective,  165 


INDEX. 


669 


Tissues,  lymphatic,  of  the  tongue,  331 

mesenchymal,  169 

muscle,  307,  311 

nephrogenic,  395 

osseous,  173 

premuscle,  296 

retroperitoneal,  433 

subcutaneous,  445 
Toes,  development  of,  i  54 
Tongue,  the,  321 

filiform  papillas  of,  322 

foramen  cagcum  liguae,  322 

fungiform  papillae  of,  322 

innervation  of,  469 

lingual  papillae  of,  322 

lingualis  muscle  of,  322 

practical  suggestions  for  study  of,  3  59 

tuberculum  impar,  321 

vallate  papillae  of,  323 
Tonsilla,  533 
Tonsils,  the,  331 

crypts  of,  331 

lingual,  331 

lymph  follicles  of,  331 

pharyngeal,  331 

Tooth  tumors,  developmental,  328 
Torneux,     concerning    malformations    of 

neural  tube,  619 

Tornier,   concerning  production  of  verte- 
brate monsters,  626 
Trabeculas  carneae,  232 
Trachea,  the,  365 
Tracts,  see  also  Fasciculi, 

central  tegmental,  526 

cortico-spinal,  see  Tracts  pyramidal 

Flechsig's,  473,  478,  519,  528 

from  Deiter's  nucleus,  473,  518 

from  suprasegmental  structures,  478, 

5i9 

Cowers,  473,  478,  519,  528 
gustatory  (see  also  Tractus  solitariiis), 

469,  474,  475 

olfactory,  474,  475,  512,  544 
optic,  474,  475,  512,  587 
predorsal,  474,  537 
pyramidal,   478,  479,    519,    528,    530, 

531,  565 
reticular  formation    +   ventro-lateral 

ground  bundle  system,  511 
reticulo-spinal  523 
rubro-spinal,  473,  518,  524 
secondary  and  tertiary  olfactory,  512 

optic  (see  also  Optic  nerve),  512 
spino-cerebellar   (ventral),    473,    47 

5*9,  528 

spino-tectal  and  thalamic,  478,  519 
spino-cerebellar     (dorsal),    473,    478, 

5i9,  S2^    * 

to  Deiter's  nucleus,  473 
to    suprasegmental    structures,    473, 

478.  5l8,  525  to  532 
Tractus  solitarius  (communis)  of  VII,  IX 

and  X  nerves,  469,  506,  510,  511, 

525,  528 
Tragus,  60 1 
Transparent    preparations    for    study    of 

bone,  219 


Transposition  of  the  viscera,  355 
Transverse  mesocolon,  382 
Trapezium  (bone),  205 

(of  medulla),  530 
Trapezoid,  the,  205 

area    of    His    (see     also    Preterminal 

area),  476,  548 
Tribrachius,  609 
Tricephalus,  611 
Trigeminus,  V,  nerve,  467,  469,  471 

Gasserian  ganglion,  467 

spinal  V  root,  467 
Trigonum  (bone),  217 

(brain),  548 
Triquetral  bone,  204 
Trochanters,  208 
Trochlea,  204 
Trochlear,  IV,  nerve,  469 
Trophoderm,  52,  67,  137 
Tsuda,    concerning    production    of    spina 

bifida,  626 

Tubal  pregnancy,  31,  119 
Tuber  cinereum,  540 
Tubercles,  greater,  204 

lesser,  204 
Tuberculum  of  rib,  189 

impar,  321 

of  Rolando,  531 
Tubular  form  of  blastoderm,  in  chick,  85 

in  Mammals,  89 

Tumors  of  sexual  glands,  origin  of,  615 
Tunica  albuginea,  408 

vasculosa  lentis,  579 

dartos,  445 

vaginalis  propria,  426 
Tunicates,  cleavage  in,  49 
Turbinated  bones,  196 

Twins,    equal    monochorionic,    605,    606, 
607 

free  duplicities,  605 

unequal  monochorionic,  606 
Tympanum,  600 

Ulna,  204 

Umbilical  arteries,  107 
ccelom,  339 
cord,  132,  142 

anomalies  of,  135 
in  Mammals,  in,  142 
in  man,  132 
length  of,  human,  134 
hernia,  117,  622 
ligament,  middle,  119,  404 
veins,  107 

Umbilicus,  dermal,  105 
double,  608 
intestinal,  105 
Unicornuate  uterus,  437 
Unilateral  hermaphroditism,  438 
Unipolarization   of   spinal   ganglion   cells, 

498 

Unna,  concerning  anomalies  of  hair,  452 
Uracho-vesical  fistula,  436 
Urachus,  106,  119,  404 
anomalies  of,  43  5 
Urdarmstrang,  70 
Ureters,  the,  394 


670 


INDEX. 


Ureters,  anomalies  of,  434 

relations  of,  to  cardinal  veins,  260 
Urethra,  the,  404,  428 

anomalies  of,  436 
Urinary  bladder,  the,  403,  404 
"Urinary  fistula,"  119 
Urogenital  sinus,  the,  403 

system,  the,  387 
anomalies  of,  433 
development  of  suprarenal  glands, 

43° 

genital  glands,  406 
kidney,  394 
mesonephros,  389 
metanephros,  394 
practical  suggestions  for  study  of, 

439 

pronephros,  387 
urethra,  403 
urinary  bladder,  403 
urogenital  sinus,  403 
Urorectal  fold,  the,  403 
Uterus,  the,  419 

anomalies  of,  437 
fixation  of  ovum  to,  120 
relation  of  placenta  to,  115 
bicornuate,  437 
bipartite,  437 
didelphys,  437 
infantile,  437 
masculinus,  421 
unicornuate,  437 
Utricle,  596 

Utriculosaccular  duct,  596 
Utriculus  prostaticus,  421 
Uvula,  533 

Vacuole,  2 

Vacuolization  of  cells  of  blastula,  52 

Vagina,  the,  419 

anomalies  of,  437 
Vagus,  X,  nerve,  469,  471 
Valves,  the,  231 

anomalies  of,  285 
Valvula  bicuspidalis,  232 

mitralis,  232 

sinus  coronarii,  232 

tricuspidalis,  232 

venae  cavse  inferioris,  232 
Valvulae  semilunares  aortas,  233 

semilunares  arteria3  pulmonalis,   233 

venosae,  231 
Vas  deferens,  420 

epididymis,  427 
Vasa  aberrantia,  351,  427 

efferentia,  420 

Vascular      system,     anomalies     of,     285, 
607 

arteries,  243 

blood  vessels,  222,  235 

blood  and  blood  cells,  270 

changes  in  the  circulation   at  birth, 
267 

development  of  the,  222 

heart,  222 

histogenesis  of  blood  cells,  270 

lymphatic  system,  276 


Vascular  system,  practical  suggestion  for 
study  of,  289 

veins,  253 

Vegetative  pole  (macromere),  56 
Veins,  accessory  hemiazygos,  262 

anomalies  of,  288,  607 

ascending  lumbar,  262 

axillary,  266 

azygos,  262 

basilic,  266 

brachial,  266 

cardinal,  253,  255,  257 

cavernous,  282,  284 

cephalic,  266 

cerebral,  2  54 

common  iliac,  261 

femoral,  267 

fibular,  266 

hemiazygos,  262 

hepatic,  265 

inferior  sagittal,  255 

internal  spermatic,  261 

jugular,  255,  256,  257 

jugulocephalic,  266 

lateralis  capitis,  2  54 

of  Galen,  255 

omphalomesenteric,  106,  238,  253 

ovarian,  261 

portal,  265 

primary  ulnar,  266 

radial,  266 

renal,  260 

revehent,  258 

saphenous,  267 

sciatic,  267 

subcardinal,  2  58 

subclavian,  256,  266 

subintestinal,  75 

supracardinal,  261 

suprarenal,  262 

testicular,  261 

their  relation  to  lymphatic  vessels,  279 

tibial,  266,  267 

umbilical,  107,  243,  253 

vitelline,  106,  238 
Velum,  anterior  medullary,  533 

posterior  medullary,  520,  533 

transversum,  461,  541 
Vena  cava,  257 

inferior,  231,  257,  260 

superior,  231 
Veno-lymphatics,  277 
Ventral  cephalic  fold  of  brain,  460 

mesentery,  379 

mesogastrium,  379 

root  fibers,  see  Efferent  root  fibers 
Ventricle,  363 

of  Verga,  559 
Ventricles  of  the  brain,  463 

fourth,  463,  485 

lateral,  463,  549 

anterior  horn  of,  549 
descending  horn  of,  549 
posterior  horn  of,  549 

third,  463,  485 
Ventricular  septum,  229 
Ventro-lateral  plate,  see  Basal  plate 
Vermiform  appendix,  342 


INDEX. 


Vermis,  533 

Vernix  caseosa,  444,  449 

Vertebras,  the,  183 

alternation  of  vertebrae   and  myoto- 
mes,  184 

anomalies  of,  213 

blastemal  stage  of,  184 

bodies  of,  184 

cartilaginous  stage  of,  184 

costal  process,  184 

intervertebral  fibrocartilage,  184 

ligaments  of,  188 

ossification  stage,  186 

practical  suggestions  for  further  study 
of,  218 

sclerotomes  of,  182 
Vertebras  cervical,  defects  of,  616 
Vertebral  arch,  184 

articular  process  of,  186 

spinous  process  of,  186 

transverse  process  of,  186 
Vertebrate,  the  definition  of,  457 

differentiation  of  the  anterior  end  of, 

457 

nervous   system,  see  Nervous  system, 

vertebrate. 
Vesical  fissure,  436 
Vesicle,  auditory,  592 

blastodermic,  138 

optic,  144,  574 
Vesicles,  brain,  461,  480 

seminal,  420 
Vestibular  ganglion  cells,  599 

membrane  (of  Reissner),  597 

nerve,  599 

part  of  acoustic  (auditory)  nerve,  469 
descending  root  of,  469 

pouch,  593 
Vestibule,  467 
Vestibulum  vaginas,  428 
Vicq  d'Azyr's  bundle,  544 
Vignal,    concerning    the    myelin    sheath, 

501  . 
Villi,  chorionic,  114,  122 

fastening,  127 

floating,  127 
Visceral  mesoderm,  75,  87 

musculature,  see  Musculature  visceral 

neurones,  sympathetic,  458 

or  splanchnic  structures,  465 
Visual  area  of  pallium,  477,  564,  565 

cortex,  564 
Vitelline  arteries,  105,  239 

circulation,  239,  242 

duct,  117 

membrane,  1 1 

veins,  106,  238 
Vitellus,  1 1 
Vitreous,  585 

humor,  585 
Vocal  cords,  superior,  or  false,  363 

true,  363 

Volar  arch,  superficial,  252 
Voluntary   muscle,    striated,    histogenesis 
of,  3°7 

origin  of,  293,  294 
Vomer,  196,  198 

43 


Von  Baer,  XIII 

concerning  cell  differentiation,  55 

Von  Baer's  law,  387 

Von  Loewenhoek,  concerning  the  dis- 
covery of  the  spermatozoon, 
XIII 

Von  Spec's  embryo,  90,  140 

"  Waters,  "  the,  117 

Wax  reconstruction,  638 

Webs  between  digits,  155 

Weigert's  haematoxylin,  635 

method  for  staining  myelin  sheaths, 
57o 

Weisman  and  Brooks,  concerning  fertili- 
zation, 40 

Wharton's  jelly,  133 

Wheeler,  diagram  showing  amitosis,  4 

White  columns  (see  also  Dorsal  fumculus), 

5ro 
matter  of  cerebral  hemispheres,  561 

of  cord  and  segmental  brain,  511 
ramus  communicans,  494,  499 
Wiedersheim,    concerning   the    mammary 

gland,  450 
Wilson,   E.    B.,  concerning  determination 

of  sex,  416,  439 
concerning     duplicity     with     double 

gastrulation,  612 
concerning  the  fertilization  of  eggs  of 

sea-urchin,  37 
Wilson,    J.    F.,    concerning    intermediate 

region  in  the  cord,  53 1 
concerning  intermediate  plate,  53 1 
Winslow,  foramen  of,  380 
Wirsung,  duct  of,  352 
Wlassak,   concerning  the  myelin  sheath, 

501 
Wolffian  duct,  389 

ridge,  391 
"Wolf's  snout,"  216 

theory  of  epigenesis,  XIII 
Woods,  concerning  sex  cells,  407 
Wright,  concerning  blood  plates,  276 

Xiphopagus,  609 
Xiphoid  process,  190 

malformations  of,  609 

Yolk,  comparison  of  amount  of  in  forms 

of  gastrulation,  61,  68 
entoderm,  in  Amphibians,  58 
in  Birds,  64 

in  Mammals,  70,  72,  85 
granules,  1 2 

lack  of,  in  Mammals,  108 
plug,  58 
sac,  103,  139 

formation  of  in  chick,  103 
function  of,  104 
in  Mammals,  108,  110 
in  man,  91,  117 

its  relation  to  blood  vessels,  242 
roof  of,  in  chick,  84,  85 
in  Mammals,  89 
in  man,  91 
stalk,  104,  in,  141,  318 


672  INDEX. 

Zander,  concerning  the  nails,  446  Zona  pellucida,  11,  36,  412 

Zenker's  fluid,  633  radiata,  412 

Ziegler,      concerning      malformations  of      Zonula  Zinnii,  588 

neural  tube,  619  Zonular  placenta,  114 
Ziegler's    fusion    theory    of    symmetrical      Zygomatic  bone,  198 

duplicity,  611  Zymogen  granules,  355 


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